DOCSLIB.ORG

Research Open Volume 2 Issue 1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Research Open Volume 2 Issue 1 Journal of Molecular Genetics Research Open Volume 2 Issue 1 Research Article Impact of MTNR1B and SENP3 Gene on Male Infertility: Prediction of 3D Structural Modeling of Protein and Drug Interaction during Spermatogenesis Aprajita, Aniket K, Meenakshi Tiwari and Ajit K Saxena* Molecular Human Genetics Laboratory, Department of Pathology/ Laboratory Medicine, All India Institute of Medical Sciences-Patna, Bihar, India *Corresponding author: Dr Ajit K Saxena, Ph.D Professor and Head, Department of Pathology/ Lab Medicine, All India Institute of Medical Sciences-Patna, Bihar, India; Tel: 917781012677; Email: [email protected] Received: April 23, 2019; Accepted: April 30, 2019; Published: May 23, 2019; Abstract Melatonin Receptor 1B (MTNR1B) and Sentrin-specific protease-3 (SENP3) gene mutation plays a significant role in the functioning of Sertoli cells (SCs) and to provide nourishment for the differentiating germ cell in testis. In the present study, next gene sequencing (NGS) of infertile male showing that the mutation in MTNR1B and SENP3 genes are associated to the male infertility. To the best of our knowledge the structure of our candidate genes (MTNR1B & SENP3) are not available in literature as well as in database. Therefore, molecular modelling technique in field of structural biology becomes relevant to predict functional aspects of the genes coded protein(s). Due to lack of knowledge of 3D structures it becomes difficult to understand the physiological function and binding specificities of the ligand molecules to the target site (protein). Swiss Model is one of the best workspace for integrated Web-based modelling expert system, help to understand the known protein sequence. Ramachandran plot was constructed for minimizing the energy or ligand binding active sites. Since, lactate synthesize by SCs provides nutritional support for proliferating germ cells in the testis. On the basis of a sequence alignment, a 3D model structure has been designed for the target protein using molecular docking technique. Present study predicts the structural model of MTNR1B and SNEP3 gene coded protein and analysed the possible interaction with Methotrexate (MTX) to ligand binding. During a comparative docking scores with respect to target protein and MTX showing a strong binding strength to active sites. Interestingly, these findings may elucidate the mechanism of gene regulation of SCs mediated protein in testis, and their impact on gene- protein and drug interaction during spermatogenesis. Hence, the present study significantly contributes in designing and optimizing therapeutic strategies againstinfertility. Keywords: MTNR1B and SENP3 Gene Mutation, Protein Modelling, Methotrexate, Infertility, Sertoli Cells, Swiss Model. Introduction in all mammals, influences various physiological activities suc h as neuroendocrine function, regulation of reproduction, sexual Human testis, spermatogenesis is an inherently complicated maturation, immune regulation, thermoregulation, aging and process that produces millions of mature germ cells named sperms, antioxidant activity [4–6]. SENP3 gene is predominantly expressed in and thereby crucial part of male fertility. Spermatogenesis depends the nucleus of Sertoli and Spermatocytes in mouse testis. SENP3 gene on the promiscuous cross-talk between Sertoli cells and developing protein also compromises tight junction in Sertoli cells at the cell-cell germ cells (spermatocytes) under the intensive role of a coordinated interface by destructing the permeability function with a concomitant regulatory network composing of endocrine, paracrine, and autocrine decline in trans-epithelial electrical resistance in primary Sertoli factors [1,2]. cells. Moreover, SENP3 knockdown disrupts F-actin architecture in In the present study, we have selected Melatonin Receptor 1B Sertoli cells through intervening different signalling pathways [2]. (MTNR1B) and Sentrin- specific protease-3 (SENP3) genes showing However, the post-translational modification of proteins by ubiquitin- mutation in male infertility after whole exome sequencing by using like modifier SUMO is an important mechanism of SNEP3 gene to Illumina Next Generation Sequencing (NGS). These mutations are regulate transcriptional events including DNA repair and other further confirmed by Ensembl database (http://asia.ensembl.org/ biological process. SENP3 gene to regulate Sertoli cell function such Homo_sapiens/Gene/Variation_Gene/) in human genome. These as to maintains the blood testicular barrier in somniferous tubules to genes are mapped on MTNR1B on chromosome - 11 and SENP3 on stimulate and create appropriate environment for spermatogenesis chromosome -17 as well, which play an important role in germ - cells [7–9]. Therefore, the study of MTNR1B and SNEP3 gene mutation proliferation during spermatogenesis and maintain male fertility. The become relevant to correlate with the reference functioning of “Sertoli mutation of MTNR1B has been associated in male infertile cases [1,3]. cell only syndrome” in the cases of male infertility with abnormal MTNR1B transcribed to Melatonin (N-acetyl-5-methoxytryptamine), karyotypes (XXY/XYY) due to non-disjunction event during meiosis a neuro-hormone that is mainly secreted from the pineal gland I of spermatogenesis in testis [10]. J Mol Genet, Volume 2(1): 1–8, 2019 Ajit K Saxena (2019) Impact of MTNR1B and SENP3 Gene on Male Infertility: Prediction of 3D Structural Modeling of Protein and Drug Interaction during Spermatogenesis The rationale behind this study to recognize the impact of gene - ii) Template Search: Identify evolutionarily related proteins with protein and drug interaction using 3D modelled structure to explore experimentally solved structures mapping corresponding residues the mechanism of infertility during spermatogenesis. The Molecular of target sequence and template structure search through BLAST Docking (MD) is to give a best way to prediction of the ligand- [14] and HHBlits has been performed against the SWISS-MODEL binding protein complex structure using computational methods template library. (https://swissmodel.expasy.org/templates/) [15]. and MD has been the most widely employed technique for structure iii) Template Selection: After nd2 step completion, a building of based drug discovery programme [11]. The main aim is to explore homology model is the availability of one or more identical structure-based virtual knowledge for identification of “new” active template proteins whose structure has been elucidated rank by the compounds towards a particular target protein(s). Another important expected quality of the resulting models as estimated by Global aspect is the ability to handle ambiguous structure or conflicting Model Quality Estimate (GMQE), Quaternary Structure Quality information present in available structural data, which is crucial for Estimate (QSQE), and target–template sequence identity that the development of stable molecule and fully automated pipelines. selected template structure experimentally confirmed by x-ray Finally, we introduced an improved modeling engine and process crystallography or NMR with good resolution value [16,17]. increased the precision of model quality estimation and helpful in iv) Build Model: A 3D protein model is automatically generated drug designing. However, molecular docking combined with other for each selected template by first transferring conserves atom computational techniques and experimental data may be involved in coordinates as defined by the target template alignment [18]. analyzing drug metabolism to obtain significant information for drug v) Evaluate Build Model: Evaluating the quality of the resulting development program and extending the scope of ongoing project model by SWISS- MODEL, it relies on the QMEAN scoring associated structural biology. The present study may also be helpful function to quantify modelling errors and provide estimates of to explore the additional knowledge what not yet existing in the expected model accuracy [19]. literature regulating gene-protein interaction during spermatogenesis in infertility. Selection of Ligand Molecule Materials and Methods Methotrexate is antagonist of folate and have anti neoplastic with immunosuppressant properties. It is an inhibitor of tetrahydrofolate The information of MTNR1B and SENP3 gene was collected from dehydrogenase and prevents the formation of tetrahydrofolate, whole genome sequence and search protein coded sequences from necessary for synthesis of thymidylate, an essential component of Biological database (https://www.ncbi.nlm.nih.gov/protein). The 3D DNA synthesis (https://www.drugbank.ca/drugs/DB00563). Its structure of protein has not been reported in literature as well as in chemical formula is C20H22N8O5 and their molecular weight is 454.45 structural database (https://www.rcsb.org/). as shown in figure-2. Homology Modeling Identification of the binding Site If experimentally determined structure is not available in Structure - based design begins with the identification of the structural database in that condition a homology modeling is the best target molecule of a potential ligand binding site. Ideally, the target way to generate 3D structure of protein on the basis of target- template site is a pocket with a variety of potential hydrogen bond donors and alignment search with help of Sequence Database (https://www.ncbi. acceptors, hydrophobic characteristics, and molecular surface sizes. nlm.nih.gov/protein/?term=mtnr1b or senp3), Protein Data Bank
Load more

Recommended publications
  • Análise Integrativa De Perfis Transcricionais De Pacientes Com
    UNIVERSIDADE DE SÃO PAULO FACULDADE DE MEDICINA DE RIBEIRÃO PRETO PROGRAMA DE PÓS-GRADUAÇÃO EM GENÉTICA ADRIANE FEIJÓ EVANGELISTA Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas Ribeirão Preto – 2012 ADRIANE FEIJÓ EVANGELISTA Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas Tese apresentada à Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo para obtenção do título de Doutor em Ciências. Área de Concentração: Genética Orientador: Prof. Dr. Eduardo Antonio Donadi Co-orientador: Prof. Dr. Geraldo A. S. Passos Ribeirão Preto – 2012 AUTORIZO A REPRODUÇÃO E DIVULGAÇÃO TOTAL OU PARCIAL DESTE TRABALHO, POR QUALQUER MEIO CONVENCIONAL OU ELETRÔNICO, PARA FINS DE ESTUDO E PESQUISA, DESDE QUE CITADA A FONTE. FICHA CATALOGRÁFICA Evangelista, Adriane Feijó Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas. Ribeirão Preto, 2012 192p. Tese de Doutorado apresentada à Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Área de Concentração: Genética. Orientador: Donadi, Eduardo Antonio Co-orientador: Passos, Geraldo A. 1. Expressão gênica – microarrays 2. Análise bioinformática por module maps 3. Diabetes mellitus tipo 1 4. Diabetes mellitus tipo 2 5. Diabetes mellitus gestacional FOLHA DE APROVAÇÃO ADRIANE FEIJÓ EVANGELISTA Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas.
    [Show full text]
  • Supplementary Materials
    Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine
    [Show full text]
  • Progress in the Discovery of Small Molecule Modulators of Desumoylation
    Curr. Issues Mol. Biol. (2020) 35: 17-34. Progress in the Discovery of Small Molecule Modulators of DeSUMOylation Shiyao Chen, Duoling Dong, Weixiang Xin and Huchen Zhou* School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China. *Correspondence: [email protected] htps://doi.org/10.21775/cimb.035.017 Abstract protein–protein interactions, gene transcription, SUMOylation and DeSUMOylation are reversible genome integrity, and DNA replication and repair protein post-translational modifcation (PTM) (Wilkinson and Henley, 2010; Vierstra, 2012; processes involving small ubiquitin-like modifer Bailey et al., 2016). In 1995, Meluh and Koshland (SUMO) proteins. Tese processes have indis- (1995) identifed Smt3 in Saccharomyces cerevi- pensable roles in various cellular processes, such siae, which is the earliest report within this fled. as subcellular localization, gene transcription, and Two years later, based on the sequence similarity DNA replication and repair. Over the past decade, between ubiquitin and a new 11.5-kDa protein, increasing atention has been given to SUMO- ubiquitin/SMT3, the name SUMO was formally related pathways as potential therapeutic targets. proposed for the frst time (Mahajan et al., 1997). Te Sentrin/SUMO-specifc protease (SENP), Although SUMO modifcation is closely which is responsible for deSUMOylation, has related to the progression of various diseases, such been proposed as a potential therapeutic target as cancers and cardiac disorders, it has aroused in the treatment of cancers and cardiac disorders. increasing atention as a potential therapeutic target Unfortunately, no SENP inhibitor has yet reached in recent years, especially concerning the Sentrin/ clinical trials. In this review, we focus on advances SUMO-specifc protease (SENP), which is the key in the development of SENP inhibitors in the past regulator of deSUMOylation.
    [Show full text]
  • University of California, Merced
    UNIVERSITY OF CALIFORNIA, MERCED SUMOylation is a regulator of regional cell fate and genomic integrity in planarians by Manish Thiruvalluvan A dissertation submitted in satisfaction of the requirements for the degree Doctor of Philosophy in Quantitative and Systems Biology Committee in Charge: Professor Kirk Jensen, Chair Professor Jennifer Manilay, Member Professor Anna Beaudin, Member Professor Néstor J. Oviedo, Advisor 2018 i Copyright Manish Thiruvalluvan, 2018 All rights reserved ii The dissertation of Manish Thiruvalluvan is approved, and it is acceptable in quality and form for publication on microfilm and electronically: Jennifer Manilay Anna Beaudin Kirk Jensen, Chair University of California, Merced 2018 iii TABLE OF CONTENTS vi. List of figures vii. List of abbreviations viii. Acknowledgements ix. Curriculum vitae xii. Abstract 1. Introduction 1.1. Regional signals influence cell fate decisions in health and disease 1.2. SUMOylation – a type of posttranslational modification 1.3. The planarian model Schmidtea mediterranea 1.4. Research summary 2. Materials and Methods 2.1. Materials 2.1.1. Organisms 2.1.2. Selection of primers and cloning 2.1.3. Antibodies, enzymes and other reagents 2.1.4. Solutions and buffers 2.2. Methods 2.2.1. Planarian husbandry 2.2.2. Identification of orthologs and phylogenetic analysis 2.2.3. PCR amplification and gel electrophoresis 2.2.4. Planarian Amputation 2.2.5. Irradiation 2.2.6. RNAi by bacteria feeding 2.2.7. Fixation protocols 2.2.8. RNA extraction 2.2.9. Planarian cell dissociation 2.2.10. Immunocytochemistry 2.2.11. RNA probe synthesis 2.2.12. In situ hybridization 2.2.13.
    [Show full text]
  • Nucleolus: a Central Hub for Nuclear Functions Olga Iarovaia, Elizaveta Minina, Eugene Sheval, Daria Onichtchouk, Svetlana Dokudovskaya, Sergey Razin, Yegor Vassetzky
    Nucleolus: A Central Hub for Nuclear Functions Olga Iarovaia, Elizaveta Minina, Eugene Sheval, Daria Onichtchouk, Svetlana Dokudovskaya, Sergey Razin, Yegor Vassetzky To cite this version: Olga Iarovaia, Elizaveta Minina, Eugene Sheval, Daria Onichtchouk, Svetlana Dokudovskaya, et al.. Nucleolus: A Central Hub for Nuclear Functions. Trends in Cell Biology, Elsevier, 2019, 29 (8), pp.647-659. 10.1016/j.tcb.2019.04.003. hal-02322927 HAL Id: hal-02322927 https://hal.archives-ouvertes.fr/hal-02322927 Submitted on 18 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Nucleolus: A Central Hub for Nuclear Functions Olga Iarovaia, Elizaveta Minina, Eugene Sheval, Daria Onichtchouk, Svetlana Dokudovskaya, Sergey Razin, Yegor Vassetzky To cite this version: Olga Iarovaia, Elizaveta Minina, Eugene Sheval, Daria Onichtchouk, Svetlana Dokudovskaya, et al.. Nucleolus: A Central Hub for Nuclear Functions. Trends in Cell Biology, Elsevier, 2019, 29 (8), pp.647-659. 10.1016/j.tcb.2019.04.003. hal-02322927 HAL Id: hal-02322927 https://hal.archives-ouvertes.fr/hal-02322927 Submitted on 18 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not.
    [Show full text]
  • Nucleophosmin and Its Complex Network: a Possible Therapeutic Target in Hematological Diseases
    Oncogene (2011) 30, 2595–2609 & 2011 Macmillan Publishers Limited All rights reserved 0950-9232/11 www.nature.com/onc REVIEW Nucleophosmin and its complex network: a possible therapeutic target in hematological diseases E Colombo1,2, M Alcalay1,2 and PG Pelicci1,2 1Department of Experimental Oncology, European Institute of Oncology, Milan, Italy and 2Dipartimento di Medicina, Chirurgia e Odontoiatria, University of Milano, Milan, Italy Nucleophosmin (NPM, also known as B23, numatrin or alternative splicing of the NPM1 transcript, have been NO38) is a ubiquitously expressed phosphoprotein belong- reported (Wang et al., 1993) (Figure 1). In the long ing to the nucleoplasmin family of chaperones. NPM is isoform, known as B23.1, exon 9 is spliced to exon 11 mainly localized in the nucleolus where it exerts many of and the coding sequence stops at exon 12, resulting in a its functions, but a proportion of the protein continuously protein of 294 residues. In the short isoform, B23.2, shuttles between the nucleus and the cytoplasm. A growing exon 9 is spliced to exon 10 that immediately contains a number of cellular proteins have been described as stop codon, and as a result, B23.2 is a truncated protein physical interactors of NPM, and consequently, NPM is of 259 residues. The prevalent form expressed in all thought to have a relevant role in diverse cellular tissues is B23.1, although the biological significance and functions, including ribosome biogenesis, centrosome physiological function of B23.2 remain largely unclear. In duplication, DNA repair and response to stress. NPM the human EST database a further transcript variant that has been implicated in the pathogenesis of several human lacks exon 8 has been identified (GenBank accession malignancies and intriguingly, it has been described both number: NM_199185).
    [Show full text]
  • ORM-Like Protein (ORMDL) – Annäherung an Die Funktion Über Die Interaktion
    ORM-like protein (ORMDL) - Annäherung an die Funktion über die Interaktion Julian Klingbeil München 2019 Aus der Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital der Ludwig–Maximilians–Universität München Direktor: Prof. Dr. med. Dr. sci. nat. C. Klein ORM-like protein (ORMDL) – Annäherung an die Funktion über die Interaktion Dissertation zum Erwerb des Doktorgrades der Medizin an der Medizinischen Fakultät der Ludwig–Maximilians–Universität zu München vorgelegt von Julian Malte Klingbeil aus Berlin 2019 Mit Genehmigung der Medizinischen Fakultät der Universität München Berichterstatterin: Prof. Dr. Ania Muntau Mitberichterstatter: Prof. Dr. Katja Radon PD Dr. Anne Hilgendorff Prof. Dr. Jürgen Behr Prof. Dr. Ortrud Steinlein Mitbetreuung durch den promovierten Mitarbeiter: Prof. Dr. Søren Gersting Dekan: Prof. Dr. med. dent. Reinhard Hickel Tag der mündlichen Prüfung: 10.10.2019 Inhaltsverzeichnis Zusammenfassung xiii 1 Einleitung 1 1.1 Asthma bronchiale . .1 1.1.1 Epidemiologie, Pathogenese und Klassifikation . .2 1.1.2 Therapie . .4 1.1.3 Gen-Umwelt-Interaktionen und Genomweite Assoziationsstudien5 1.2 Das neue Asthma-Risikogen ORMDL . .8 1.3 Der β2-Adrenorezeptor . 11 1.4 Protein-Protein-Interaktionen . 13 1.4.1 Biolumineszenz-Resonanz-Energie-Transfer . 15 1.5 Zielsetzung der Arbeit . 18 2 Material und Methoden 19 2.1 Material . 19 2.1.1 Laborgeräte . 19 2.1.2 Allgemeine Verbrauchsmaterialien, Chemikalien und Reagenzien . 21 2.1.3 Lösungen, Reagenzien-Kits und Puffer . 26 2.1.4 Medium . 28 2.1.5 Zelllinien und Bakterienstämme . 28 2.1.6 Antikörper . 29 2.1.7 β-Sympathomimetika . 29 2.1.8 Restriktionsenzyme . 30 2.1.9 Vektoren und DNA .
    [Show full text]
  • Systematic Discovery of Endogenous Human Ribonucleoprotein Complexes
    bioRxiv preprint doi: https://doi.org/10.1101/480061; this version posted November 27, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Systematic discovery of endogenous human ribonucleoprotein complexes Anna L. Mallam1,2,3,§,*, Wisath Sae-Lee1,2,3, Jeffrey M. Schaub1,2,3, Fan Tu1,2,3, Anna Battenhouse1,2,3, Yu Jin Jang1, Jonghwan Kim1, Ilya J. Finkelstein1,2,3, Edward M. Marcotte1,2,3,§, Kevin Drew1,2,3,§,* 1 Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA 2 Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX 78712, USA 3 Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA § Correspondence: [email protected] (A.L.M.), [email protected] (E.M.M.), [email protected] (K.D.) * These authors contributed equally to this work Short title: A resource of human ribonucleoprotein complexes Summary: An exploration of human protein complexes in the presence and absence of RNA reveals endogenous ribonucleoprotein complexes ! 1! bioRxiv preprint doi: https://doi.org/10.1101/480061; this version posted November 27, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Abstract Ribonucleoprotein (RNP) complexes are important for many cellular functions but their prevalence has not been systematically investigated.
    [Show full text]
  • Global Screening of Sentrin-Specific Protease Family Substrates in Sumoylation
    bioRxiv preprint doi: https://doi.org/10.1101/2020.02.25.964072; this version posted February 26, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Global Screening of Sentrin-Specific Protease Family Substrates in SUMOylation Yunzhi Wang, 1, 4 Xiaohui Wu,1, 4 Rui Ge,1, 4 Lei Song, 2 Kai Li, 2 Sha Tian,1 Lili Cai, 1 Mingwei Liu, 2 Wenhao Shi, 2Guoying Yu, 3 Bei Zhen, 2 Yi Wang, 2 Fuchu He, 1, 2, * Jun Qin, 1, 2, * Chen Ding1, 2, * 1State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Zhongshan Hospital, Fudan University, Shanghai, 200432, China 2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206, China 3State Key Laboratory of Cell Differentiation and Regulation, College of Life Science, Henan Normal University, Xinxiang, Henan 453007 4Co-first author *Correspondence: [email protected] (C.D.); [email protected] (J.Q.); [email protected] (F.H.); Key Words 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.02.25.964072; this version posted February 26, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Posttranslational modification; SUMO; Sentrin/SUMO-specific proteases; Mass Spectrometry; Innate Immunity Abstract Post-translational modification of proteins by the addition of small ubiquitin-related modifier (SUMO) is a dynamic process, in which deSUMOylation is carried out by members of the Sentrin/SUMO-specific protease (SENP) family.
    [Show full text]
  • The Unique Brucella Effectors Nyxa and Nyxb Target SENP3 to Modulate the Subcellular Localisation of Nucleolar Proteins
    bioRxiv preprint doi: https://doi.org/10.1101/2021.04.23.441069; this version posted April 23, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. The unique Brucella effectors NyxA and NyxB target SENP3 to modulate the subcellular localisation of nucleolar proteins Artur Louche1, Amandine Blanco1, Thais Lourdes Santos Lacerda1, Claire Lionnet2, Célia Bergé1, Monica Rolando3, Frédérique Lembo4, Jean-Paul Borg4,5, Carmen Buchrieser3, Masami Nagahama6, Jean-Pierre Gorvel7, Virginie Gueguen-Chaignon8, Laurent Terradot1, , and Suzana P. Salcedo1, 1Laboratory of Molecular Microbiology and Structural Biochemistry, Centre National de la Recherche Scientifique UMR5086, Université de Lyon, Lyon, France 2Laboratoire de Reproduction et Developpement des Plantes, Universite de Lyon, ENS de Lyon, UCBL, INRA, CNRS, Lyon, France 3Institut Pasteur, Biologie des Bactéries Intracellulaires, CNRS UMR 3525, Paris, France 4Aix-Marseille Université, Inserm, Institut Paoli-Calmettes, CNRS, Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France 5Institut Universitaire de France 6Laboratory of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, Tokyo, Japan 7Aix-Marseille Univ, CNRS, INSERM, CIML, Marseille, France 8Protein Science Facility, SFR Biosciences, Centre National de la Recherche Scientifique UAR3444, Université de Lyon, Lyon, France The cell nucleus is a primary target for intracellular bacterial SENP3 functions as a processing enzyme for the SUMO2/3 pathogens to counteract immune responses and hijack host sig- precursor and as a deconjugase of SUMOylated substrates. nalling pathways to cause disease.
    [Show full text]
  • The Role of Ubiquitination and Sumoylation in DNA Replication
    The Role of Ubiquitination and SUMOylation in DNA Replication Tarek Abbas1,2,3* 1Department of Radiation Oncology, University of Virginia, Charlotesville, VA, USA. 2Department of Biochemistry and Molecular Genetics, University of Virginia, Charlotesville, VA, USA. 3Center for Cell Signaling, University of Virginia, Charlotesville, VA, USA. *Correspondence: [email protected] htps://doi.org/10.21775/cimb.040.189 Abstract Regulation of eukaryotic DNA DNA replication is a tightly regulated conserved replication process that ensures the faithful transmission of genetic material to defne heritable phenotypic Initiation of DNA replication traits. Perturbations in this process result in Eukaryotic DNA replication is tightly regulated genomic instability, mutagenesis, and diseases, such that cells replicate their entire genome once including malignancy. Proteins involved in the and only once in a given cell cycle (Machida et initiation, progression, and termination of DNA al., 2005). For mammalian cells, this is no easy replication are subject to a plethora of revers- task since each proliferative somatic cell must ef- ible post-translational modifcations (PTMs) to ciently replicate approximately 6 billion base pairs provide a proper temporal and spatial control (in male cells) from roughly 250,000 replication of replication. Among these, modifcations origins scatered throughout the genome with involving the covalent atachment of the small each division cycle (Cadoret et al., 2008; Sequeira- protein ubiquitin or the small ubiquitin-like Mendes et al., 2009; Karnani et al., 2010). With modifer (SUMO) to replication and replication- roughly 600 million new blood cells born in the associated proteins are particularly important for bone marrow of an adult human (Doulatov et al., the proper regulation of DNA replication as well 2012), one cannot grasp the magnitude of the as for optimal cellular responses to replication task the replication machinery has to accomplish.
    [Show full text]
  • Variation in Protein Coding Genes Identifies Information Flow
    bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Animal complexity and information flow 1 1 2 3 4 5 Variation in protein coding genes identifies information flow as a contributor to 6 animal complexity 7 8 Jack Dean, Daniela Lopes Cardoso and Colin Sharpe* 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Institute of Biological and Biomedical Sciences 25 School of Biological Science 26 University of Portsmouth, 27 Portsmouth, UK 28 PO16 7YH 29 30 * Author for correspondence 31 [email protected] 32 33 Orcid numbers: 34 DLC: 0000-0003-2683-1745 35 CS: 0000-0002-5022-0840 36 37 38 39 40 41 42 43 44 45 46 47 48 49 Abstract bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Animal complexity and information flow 2 1 Across the metazoans there is a trend towards greater organismal complexity. How 2 complexity is generated, however, is uncertain. Since C.elegans and humans have 3 approximately the same number of genes, the explanation will depend on how genes are 4 used, rather than their absolute number.
    [Show full text]