The Splicing Factor XAB2 Interacts with ERCC1-XPF and XPG for RNA-Loop Processing During Mammalian Development
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Control of Protein Function
3 Control of Protein Function In the cell, precise regulation of protein function is essential to avoid chaos. This chapter describes the most important molecular mechanisms by which protein function is regulated in cells. These range from control of a protein’s location and lifetime within the cell to the binding of regulatory molecules and covalent modifications such as phosphorylation that rapidly switch protein activity on or off. Also covered here are the nucleotide-driven switches in conformation that underlie the action of motor proteins and that regulate many signal transduction pathways. 3-0 Overview: Mechanisms of Regulation 3-1 Protein Interaction Domains 3-2 Regulation by Location 3-3 Control by pH and Redox Environment 3-4 Effector Ligands: Competitive Binding and Cooperativity 3-5 Effector Ligands: Conformational Change and Allostery 3-6 Protein Switches Based on Nucleotide Hydrolysis 3-7 GTPase Switches: Small Signaling G Proteins 3-8 GTPase Switches: Signal Relay by Heterotrimeric GTPases 3-9 GTPase Switches: Protein Synthesis 3-10 Motor Protein Switches 3-11 Regulation by Degradation 3-12 Control of Protein Function by Phosphorylation 3-13 Regulation of Signaling Protein Kinases: Activation Mechanism 3-14 Regulation of Signaling Protein Kinases: Cdk Activation 3-15 Two-Component Signaling Systems in Bacteria 3-16 Control by Proteolysis: Activation of Precursors 3-17 Protein Splicing: Autoproteolysis by Inteins 3-18 Glycosylation 3-19 Protein Targeting by Lipid Modifications 3-20 Methylation, N-acetylation, Sumoylation and Nitrosylation 3-0 Overview: Mechanisms of Regulation Protein function in living cells is precisely regulated A typical bacterial cell contains a total of about 250,000 protein molecules (comprising different amounts of each of several thousand different gene products), which are packed into a volume so small that it has been estimated that, on average, they are separated from one another by a distance that would contain only a few molecules of water. -
Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-Like Mouse Models: Tracking the Role of the Hairless Gene
University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 5-2006 Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene Yutao Liu University of Tennessee - Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Part of the Life Sciences Commons Recommended Citation Liu, Yutao, "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino- like Mouse Models: Tracking the Role of the Hairless Gene. " PhD diss., University of Tennessee, 2006. https://trace.tennessee.edu/utk_graddiss/1824 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Yutao Liu entitled "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Life Sciences. Brynn H. Voy, Major Professor We have read this dissertation and recommend its acceptance: Naima Moustaid-Moussa, Yisong Wang, Rogert Hettich Accepted for the Council: Carolyn R. -
Enzyme-Catalyzed Expressed Protein Ligation
ENZYME-CATALYZED EXPRESSED PROTEIN LIGATION by Samuel Henager A dissertation submitted to The Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland August, 2017 Abstract Expressed protein ligation involves the chemoselective reaction of recombinant protein thioesters produced via inteins with N-Cys containing synthetic peptides and has proved to be a valuable method for protein semisynthesis. Expressed protein ligation requires a cysteine residue at the ligation junction which can limit its use. Here we employ subtiligase, a re-engineered form of the protease subtilisin, to ligate a range of synthetic peptides, without the requirement of an N-terminal cysteine, to a variety of recombinant protein thioesters in rapid fashion. We have further broadened the scope of subtiligase-mediated protein ligations by employing a second-generation form (E156Q/G166K subtiligase) and a newly developed form (Y217K subtiligase) for ligation junctions with acidic residues. We have applied subtiligase-mediated expressed protein ligation to the generation of tetraphosphorylated, monophosphorylated, and non-phosphorylated forms of the tumor suppressor lipid phosphatase PTEN. In this way, we have demonstrated that the natural sequence around the ligation junction produced by subtiligase rather than cysteine-mediated ligation is necessary to confer the dramatic impact of tail phosphorylation on driving PTEN's closed conformation and reduced activity. We thus propose that subtiligase-mediated expressed protein ligation is an attractive traceless technology for precision analysis of protein post- translational modifications. Thesis Advisor: Dr. Philip Cole Second Reader: Dr. Jungsan Sohn ii To my family and friends, without whom none of this would have been possible. -
NMR Evidence for an Unusual Peptide Bond at the N-Extein–Intein Junction
Semisynthesis of a segmental isotopically labeled protein splicing precursor: NMR evidence for an unusual peptide bond at the N-extein–intein junction Alessandra Romanelli*†, Alexander Shekhtman†‡, David Cowburn‡, and Tom W. Muir*§ *Laboratory of Synthetic Protein Chemistry, The Rockefeller University, 1230 York Avenue, New York, NY 10021; and ‡New York Structure Biology Center, New York, NY 10027 Edited by Rowena G. Matthews, University of Michigan, Ann Arbor, MI, and approved March 9, 2004 (received for review October 13, 2003) Protein splicing is a posttranslational autocatalytic process in which (or O 3 N) acyl shift. This is known to be a spontaneous chemical an intervening sequence, termed an intein, is removed from a host rearrangement (10) and presumably does not require the intein. protein, the extein. Although we have a reasonable picture of the Although we have a reasonable overview of the various steps in basic chemical steps in protein splicing, our knowledge of how protein splicing, the mechanistic details of autocatalysis remain these are catalyzed and regulated is less well developed. In the poorly understood. There have been several high-resolution crystal current study, a combination of NMR spectroscopy and segmental structures of inteins (11–16) and related proteins (5, 7, 17). These isotopic labeling has been used to study the structure of an active structures have shed some light on the mechanism of the first step protein splicing precursor, corresponding to an N-extein fusion of in protein splicing, the N 3 S (or N 3 O) acyl shift. As illustrated ؊ 1 the Mxe GyrA intein. The JNC coupling constant for the ( 1) in Fig. -
Visual Exploration Across Biomedical Databases
1 Visual Exploration Across Biomedical Databases Michael D. Lieberman∗†‡ Sima Taheri∗ Huimin Guo∗ Fatemeh Mir-Rashed∗ [email protected] [email protected] [email protected] [email protected] Inbal Yahav§ Aleks Aris∗ Ben Shneiderman∗† [email protected] [email protected] [email protected] Abstract—Though biomedical research often draws on knowl- mentioned in d. d may also have associations with other edge from a wide variety of fields, few visualization methods PubMed documents that cite d as a reference, as well as for biomedical data incorporate meaningful cross-database ex- associations to the PubMed documents that d itself cites. ploration. A new approach is offered for visualizing and explor- ∈ ing a query-based subset of multiple heterogeneous biomedical Furthermore, each gene g G could have associations with databases. Databases are modeled as an entity-relation graph the proteins for which g codes, or the DNA sequences in containing nodes (database records) and links (relationships which g’s code appears. Usually, the various types of records between records). Users specify a keyword search string to in these databases also have many attributes associated with retrieve an initial set of nodes, and then explore intra- and inter- them. For example, PubMed documents might be annotated database links. Results are visualized with user-defined semantic substrates to take advantage of the rich set of attributes usually with the date of publication, authors, and general topics, while present in biomedical data. Comments from domain experts gene records could be annotated with the relevant species, indicate that this visualization method is potentially advantageous location on chromosome, or function. -
Site Selection of Pyrococcus Horikoshi Rada Intein
Murray State's Digital Commons Honors College Theses Honors College Spring 5-8-2020 Site Selection of Pyrococcus horikoshi RadA Intein Madison Paige White Murray State University Follow this and additional works at: https://digitalcommons.murraystate.edu/honorstheses Part of the Biology Commons, and the Microbiology Commons Recommended Citation White, Madison Paige, "Site Selection of Pyrococcus horikoshi RadA Intein" (2020). Honors College Theses. 44. https://digitalcommons.murraystate.edu/honorstheses/44 This Thesis is brought to you for free and open access by the Honors College at Murray State's Digital Commons. It has been accepted for inclusion in Honors College Theses by an authorized administrator of Murray State's Digital Commons. For more information, please contact [email protected]. Murray State University Honors College HONORS THESIS Certificate of Approval Site Selection of Pyrococcus horikoshi RadA Intein Madison White May/2021 Approved to fulfill the _________________________________________ requirements of HON 437 Dr. Christopher Lennon, Assistant Professor Biology Approved to fulfill the _________________________________________ Honors Thesis requirement Dr. Warren Edminster, Executive Director of the Murray State Honors Honors College Diploma Examination Approval Page Author: Madison White Project Title: Site Selection of Pyrococcus horikoshi RadA Intein Department: Biology Date of Defence: April 24, 2020 Approval by Examining Committee: ____________________________________________ __________________ -
Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement. -
Expanding the Uses of Split-Intein Through Protein Engineering
Expanding The Uses of Split-Intein Through Protein Engineering by Stanley Siu Cheung Wong A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Institute of Biomaterials and Biomedical Engineering University of Toronto © Copyright by Stanley Siu Cheung Wong 2013 Expanding the Uses of Split-Intein Through Protein Engineering Stanley Siu Cheung Wong Doctor of Philosophy Institute of Biomaterials and Biomedical Engineering University of Toronto 2013 Abstract Split-protein systems are invaluable tools used for the discovery and investigations of the complexities of protein functions and interactions. Split-protein systems rely on the non-covalent interactions of two fragments of a split protein to restore protein function. Because of this, they have the ability to restore protein functions post-translationally, thus allowing for quick and efficient responses to a milieu of cellular mechanisms. Despite this, split-protein systems ha ve been largely limited as a reporting tool for protein-protein interactions. The recent discovery of inteins has the potential of broadening the scope of split-protein systems. Inteins are protein elements that possess the unique ability of post-translationally ligating protein fragments together with a native peptide bond, a process termed protein splicing. This allows split-proteins to reassemble in a more natural state. Exploiting this property and utilizing protein engineering techniques and methodologies, several approaches are described here for restoring and controlling split-protein functions using inteins. ii First, the protein splicing behaviour was demonstrated with the development of a simple in vitro visual fluorescence assay that relies on examining the subcellular localization of different fluorescent proteins. -
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. -
Unit 6-Nucleus
Unit 6-Nucleus Dr. Pallee shree Nucleus • Nucleus is the most important organelle in the cell • It distinguishes eukaryotic from prokaryotic cells • By housing the cell's genome, the nucleus serves both as the repository of genetic information and as the cell's control center • DNA replication, transcription, and RNA processing all take place within the nucleus Cont… • A nucleus is a double-membraned eukaryotic cell organelle that contains the genetic material. • It appears in an oval shape averages 5µm in width. • It often lies in the centre of a cell • The nucleus was the first organelle to be discovered • Nuclei 1st discovered and named by Robert Brown • Role of nucleus 1st demonestrated by Max Hammerling Ultra structure of Nucleus 1. Nuclear envelope 2. nuclear pores 3. Nucleoplasm 4. Nucleolus 5. Chromosomes 1. Structure of Nuclear envelope • The nuclear envelope has a complex structure consisting of a) Two nuclear membranes separated by a perinuclear space measuring about 20–40 nm across b) Underlying nuclear lamina • The nucleus is surrounded by a system of two concentric membranes, called the inner and outer nuclear membranes • The inner and outer nuclear membranes are joined at nuclear pore complexes a. Nuclear membranes • The outer nuclear membrane is continuous with the endoplasmic reticulum, so the space between the • The critical function of the inner and outer nuclear membranes nuclear membranes is to act as is directly connected with the lumen a barrier that separates the of the ER contents of the nucleus from the cytoplasm. • It is functionally similar to the membranes of the ER and has • Like other cell membranes, ribosomes bound to its cytoplasmic each nuclear membrane is a surface but protein composition phospholipid bilayer differ slightly as they are enriched in permeable only to small proteins which binds to cytoskeleton nonpolar molecules • The inner nuclear membrane carries • Other molecules are unable to proteins that are specific to the diffuse through the bilayer. -
Open Data for Differential Network Analysis in Glioma
International Journal of Molecular Sciences Article Open Data for Differential Network Analysis in Glioma , Claire Jean-Quartier * y , Fleur Jeanquartier y and Andreas Holzinger Holzinger Group HCI-KDD, Institute for Medical Informatics, Statistics and Documentation, Medical University Graz, Auenbruggerplatz 2/V, 8036 Graz, Austria; [email protected] (F.J.); [email protected] (A.H.) * Correspondence: [email protected] These authors contributed equally to this work. y Received: 27 October 2019; Accepted: 3 January 2020; Published: 15 January 2020 Abstract: The complexity of cancer diseases demands bioinformatic techniques and translational research based on big data and personalized medicine. Open data enables researchers to accelerate cancer studies, save resources and foster collaboration. Several tools and programming approaches are available for analyzing data, including annotation, clustering, comparison and extrapolation, merging, enrichment, functional association and statistics. We exploit openly available data via cancer gene expression analysis, we apply refinement as well as enrichment analysis via gene ontology and conclude with graph-based visualization of involved protein interaction networks as a basis for signaling. The different databases allowed for the construction of huge networks or specified ones consisting of high-confidence interactions only. Several genes associated to glioma were isolated via a network analysis from top hub nodes as well as from an outlier analysis. The latter approach highlights a mitogen-activated protein kinase next to a member of histondeacetylases and a protein phosphatase as genes uncommonly associated with glioma. Cluster analysis from top hub nodes lists several identified glioma-associated gene products to function within protein complexes, including epidermal growth factors as well as cell cycle proteins or RAS proto-oncogenes. -
Genome-Wide DNA Methylation Profiles in Community Members Exposed to the World Trade Center Disaster
International Journal of Environmental Research and Public Health Article Genome-Wide DNA Methylation Profiles in Community Members Exposed to the World Trade Center Disaster Alan A. Arslan 1,2,3,* , Stephanie Tuminello 2, Lei Yang 2, Yian Zhang 2, Nedim Durmus 4, Matija Snuderl 5, Adriana Heguy 5,6, Anne Zeleniuch-Jacquotte 2,3, Yongzhao Shao 2,3 and Joan Reibman 4 1 Department of Obstetrics and Gynecology, New York University Langone Health, New York, NY 10016, USA 2 Department of Population Health, New York University Langone Health, New York, NY 10016, USA; [email protected] (S.T.); [email protected] (L.Y.); [email protected] (Y.Z.); [email protected] (A.Z.-J.); [email protected] (Y.S.) 3 NYU Perlmutter Comprehensive Cancer Center, New York, NY 10016, USA 4 Department of Medicine, New York University Langone Health, New York, NY 10016, USA; [email protected] (N.D.); [email protected] (J.R.) 5 Department of Pathology, New York University Langone Health, New York, NY 10016, USA; [email protected] (M.S.); [email protected] (A.H.) 6 NYU Langone’s Genome Technology Center, New York, NY 10016, USA * Correspondence: [email protected] Received: 30 June 2020; Accepted: 25 July 2020; Published: 30 July 2020 Abstract: The primary goal of this pilot study was to assess feasibility of studies among local community members to address the hypothesis that complex exposures to the World Trade Center (WTC) dust and fumes resulted in long-term epigenetic changes. We enrolled 18 WTC-exposed cancer-free women from the WTC Environmental Health Center (WTC EHC) who agreed to donate blood samples during their standard clinical visits.