Molecular Mechanism of Membrane Targeting by the GRP1 PH Domain
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Structure and Function of the Fgd Family of Divergent FYVE Domain Proteins
Biochemistry and Cell Biology Structure and Function of the Fgd Family of Divergent FYVE Domain Proteins Journal: Biochemistry and Cell Biology Manuscript ID bcb-2018-0185.R1 Manuscript Type: Mini Review Date Submitted by the 03-Aug-2018 Author: Complete List of Authors: Eitzen, Gary; University of Alberta Faculty of Medicine and Dentistry Smithers, Cameron C.; University of Alberta, Biochemistry Murray, Allan; University of Alberta Faculty of Medicine and Dentistry Overduin, Michael; University of Alberta Faculty of Medicine and Dentistry Draft Fgd, Pleckstrin Homology domain, FYVE domain, Dbl Homology Domain, Keyword: Rho GEF Is the invited manuscript for consideration in a Special CSMB Special Issue Issue? : https://mc06.manuscriptcentral.com/bcb-pubs Page 1 of 37 Biochemistry and Cell Biology Title: Structure and Function of the Fgd Family of Divergent FYVE Domain Proteins Authors: Gary Eitzen1, Cameron C. Smithers2, Allan G Murray3 and Michael Overduin2* Draft 1Department of Cell Biology, 2Department of Biochemistry, 3Department of Medicine, University of Alberta, Edmonton, Alberta, Canada *Corresponding author. Michael Overduin Telephone: +1 780 492 3518 Fax: +1 780 492-0886 E-mail: [email protected] https://mc06.manuscriptcentral.com/bcb-pubs Biochemistry and Cell Biology Page 2 of 37 Abstract FYVE domains are highly conserved protein modules that typically bind phosphatidylinositol 3-phosphate (PI3P) on the surface of early endosomes. Along with pleckstrin homology (PH) and phox homology (PX) domains, FYVE domains are the principal readers of the phosphoinositide (PI) code that mediate specific recognition of eukaryotic organelles. Of all the human FYVE domain-containing proteins, those within the Faciogenital dysplasia (Fgd) subfamily are particularly divergent, and couple with GTPases to exert unique cellular functions. -
Sorting Nexins in Protein Homeostasis Sara E. Hanley1,And Katrina F
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 6 November 2020 doi:10.20944/preprints202011.0241.v1 Sorting nexins in protein homeostasis Sara E. Hanley1,and Katrina F. Cooper2* 1Department of Molecular Biology, Graduate School of Biomedical Sciences, Rowan University, Stratford, NJ, 08084, USA 1 [email protected] 2 [email protected] * [email protected] Tel: +1 (856)-566-2887 1Department of Molecular Biology, Graduate School of Biomedical Sciences, Rowan University, Stratford, NJ, 08084, USA Abstract: Sorting nexins (SNXs) are a highly conserved membrane-associated protein family that plays a role in regulating protein homeostasis. This family of proteins is unified by their characteristic phox (PX) phosphoinositides binding domain. Along with binding to membranes, this family of SNXs also comprises a diverse array of protein-protein interaction motifs that are required for cellular sorting and protein trafficking. SNXs play a role in maintaining the integrity of the proteome which is essential for regulating multiple fundamental processes such as cell cycle progression, transcription, metabolism, and stress response. To tightly regulate these processes proteins must be expressed and degraded in the correct location and at the correct time. The cell employs several proteolysis mechanisms to ensure that proteins are selectively degraded at the appropriate spatiotemporal conditions. SNXs play a role in ubiquitin-mediated protein homeostasis at multiple levels including cargo localization, recycling, degradation, and function. In this review, we will discuss the role of SNXs in three different protein homeostasis systems: endocytosis lysosomal, the ubiquitin-proteasomal, and the autophagy-lysosomal system. The highly conserved nature of this protein family by beginning with the early research on SNXs and protein trafficking in yeast and lead into their important roles in mammalian systems. -
Structural and Functional Insights Into Sorting Nexin 5/6 Interaction with Bacterial Effector Ince
OPEN Citation: Signal Transduction and Targeted Therapy (2017) 2, e17030; doi:10.1038/sigtrans.2017.30 www.nature.com/sigtrans ARTICLE Structural and functional insights into sorting nexin 5/6 interaction with bacterial effector IncE Qingxiang Sun1,5, Xin Yong1,2,5, Xiaodong Sun3,5, Fan Yang1,2,5, Zhonghua Dai4, Yanqiu Gong1, Liming Zhou3, Xia Zhang1, Dawen Niu1, Lunzhi Dai1, Jia-Jia Liu4 and Da Jia1,2 The endosomal trafficking pathways are essential for many cellular activities. They are also important targets by many intracellular pathogens. Key regulators of the endosomal trafficking include the retromer complex and sorting nexins (SNXs). Chlamydia trachomatis effector protein IncE directly targets the retromer components SNX5 and SNX6 and suppresses retromer-mediated transport, but the exact mechanism has remained unclear. We present the crystal structure of the PX domain of SNX5 in complex with IncE, showing that IncE binds to a highly conserved hydrophobic groove of SNX5. The unique helical hairpin of SNX5/6 is essential for binding, explaining the specificity of SNX5/6 for IncE. The SNX5/6–IncE interaction is required for cellular localization of IncE and its inhibitory function. Mechanistically, IncE inhibits the association of CI-MPR cargo with retromer-containing endosomal subdomains. Our study provides new insights into the regulation of retromer-mediated transport and illustrates the intricate competition between host and pathogens in controlling cellular trafficking. Signal Transduction and Targeted Therapy (2017) 2, e17030; doi:10.1038/sigtrans.2017.30; -
The PX Domain Protein Interaction Network in Yeast
The PX domain protein interaction network in yeast Zur Erlangung des akademischen Grades eines DOKTORS DER NATURWISSENSCHAFTEN (Dr. rer. nat.) der Fakultät für Chemie und Biowissenschaften der Universität Karlsruhe (TH) vorgelegte DISSERTATION von Dipl. Biol. Carolina S. Müller aus Buenos Aires Dekan: Prof. Dr. Manfred Kappes Referent: Dr. Nils Johnsson Korreferent: HD. Dr. Adam Bertl Tag der mündlichen Prüfung: 17.02.2005 I dedicate this work to my Parents and Alex TABLE OF CONTENTS Table of contents Introduction 1 Yeast as a model organism in proteome analysis 1 Protein-protein interactions 2 Protein Domains in Yeast 3 Classification of protein interaction domains 3 Phosphoinositides 5 Function 5 Structure 5 Biochemistry 6 Localization 7 Lipid Binding Domains 8 The PX domain 10 Function of PX domain containing proteins 10 PX domain structure and PI binding affinities 10 Yeast PX domain containing proteins 13 PX domain and protein-protein interactions 13 Lipid binding domains and protein-protein interactions 14 The PX-only proteins Grd19p and Ypt35p and their phenotypes 15 Aim of my PhD work 16 Project outline 16 Searching for interacting partners 16 Confirmation of obtained interactions via a 16 second independent method Mapping the interacting region 16 The Two-Hybrid System 17 Definition 17 Basic Principle of the classical Yeast-Two Hybrid System 17 Peptide Synthesis 18 SPOT synthesis technique 18 Analysis of protein- peptide contact sites based on SPOT synthesis 19 TABLE OF CONTENTS Experimental procedures 21 Yeast two-hybrid assay -
Membrane Insertion of the FYVE Domain Is Modulated by Ph Ju He,1 Mohsin Vora,2 Rachel M
proteins STRUCTURE O FUNCTION O BIOINFORMATICS Membrane insertion of the FYVE domain is modulated by pH Ju He,1 Mohsin Vora,2 Rachel M. Haney,2,3 Grigory S. Filonov,4 Catherine A. Musselman,1 Christopher G. Burd,5 Andrei G. Kutateladze,6 Vladislav V. Verkhusha,4 Robert V. Stahelin,2,3,7* and Tatiana G. Kutateladze1* 1 Department of Pharmacology, University of Colorado Denver School of Medicine, Aurora, Colorado 80045 2 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, Indiana 46617 3 Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556 4 Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461 5 Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6 Department of Chemistry and Biochemistry, University of Denver, Denver, Colorado 80210 7 The Walther Center for Cancer Research, University of Notre Dame, Notre Dame, Indiana 46556 INTRODUCTION ABSTRACT Phosphoinositide (PI) 3-kinases regulate membrane trafficking, pro- The FYVE domain associates with phosphati- tein sorting and signaling by generating phosphatidylinositol (PtdIns) dylinositol 3-phosphate [PtdIns(3)P] in mem- derivatives phosphorylated at the third position of the inositol ring.1,2 branes of early endosomes and penetrates bilayers. Here, we detail principles of mem- Of the four known products of PI 3-kinases, PtdIns 3-phosphate brane anchoring and show that the FYVE do- [PtdIns(3)P] is the most abundant and is constitutively produced in the main insertion into PtdIns(3)P-enriched cytosolic leaflet of membranes of early endosomes. -
Supp Table 6.Pdf
Supplementary Table 6. Processes associated to the 2037 SCL candidate target genes ID Symbol Entrez Gene Name Process NM_178114 AMIGO2 adhesion molecule with Ig-like domain 2 adhesion NM_033474 ARVCF armadillo repeat gene deletes in velocardiofacial syndrome adhesion NM_027060 BTBD9 BTB (POZ) domain containing 9 adhesion NM_001039149 CD226 CD226 molecule adhesion NM_010581 CD47 CD47 molecule adhesion NM_023370 CDH23 cadherin-like 23 adhesion NM_207298 CERCAM cerebral endothelial cell adhesion molecule adhesion NM_021719 CLDN15 claudin 15 adhesion NM_009902 CLDN3 claudin 3 adhesion NM_008779 CNTN3 contactin 3 (plasmacytoma associated) adhesion NM_015734 COL5A1 collagen, type V, alpha 1 adhesion NM_007803 CTTN cortactin adhesion NM_009142 CX3CL1 chemokine (C-X3-C motif) ligand 1 adhesion NM_031174 DSCAM Down syndrome cell adhesion molecule adhesion NM_145158 EMILIN2 elastin microfibril interfacer 2 adhesion NM_001081286 FAT1 FAT tumor suppressor homolog 1 (Drosophila) adhesion NM_001080814 FAT3 FAT tumor suppressor homolog 3 (Drosophila) adhesion NM_153795 FERMT3 fermitin family homolog 3 (Drosophila) adhesion NM_010494 ICAM2 intercellular adhesion molecule 2 adhesion NM_023892 ICAM4 (includes EG:3386) intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)adhesion NM_001001979 MEGF10 multiple EGF-like-domains 10 adhesion NM_172522 MEGF11 multiple EGF-like-domains 11 adhesion NM_010739 MUC13 mucin 13, cell surface associated adhesion NM_013610 NINJ1 ninjurin 1 adhesion NM_016718 NINJ2 ninjurin 2 adhesion NM_172932 NLGN3 neuroligin -
1 Novel Expression Signatures Identified by Transcriptional Analysis
ARD Online First, published on October 7, 2009 as 10.1136/ard.2009.108043 Ann Rheum Dis: first published as 10.1136/ard.2009.108043 on 7 October 2009. Downloaded from Novel expression signatures identified by transcriptional analysis of separated leukocyte subsets in SLE and vasculitis 1Paul A Lyons, 1Eoin F McKinney, 1Tim F Rayner, 1Alexander Hatton, 1Hayley B Woffendin, 1Maria Koukoulaki, 2Thomas C Freeman, 1David RW Jayne, 1Afzal N Chaudhry, and 1Kenneth GC Smith. 1Cambridge Institute for Medical Research and Department of Medicine, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0XY, UK 2Roslin Institute, University of Edinburgh, Roslin, Midlothian, EH25 9PS, UK Correspondence should be addressed to Dr Paul Lyons or Prof Kenneth Smith, Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0XY, UK. Telephone: +44 1223 762642, Fax: +44 1223 762640, E-mail: [email protected] or [email protected] Key words: Gene expression, autoimmune disease, SLE, vasculitis Word count: 2,906 The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non-exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article (if accepted) to be published in Annals of the Rheumatic Diseases and any other BMJPGL products to exploit all subsidiary rights, as set out in their licence (http://ard.bmj.com/ifora/licence.pdf). http://ard.bmj.com/ on September 29, 2021 by guest. Protected copyright. 1 Copyright Article author (or their employer) 2009. -
Embo Embo Embo
The EMBO Journal (2007) 26, 3709–3719 | & 2007 European Molecular Biology Organization | All Rights Reserved 0261-4189/07 www.embojournal.org TTHEH E EEMBOMBO JJOURNALOURN AL The structural basis of novel endosome anchoring activity of KIF16B kinesin Nichole R Blatner1, Michael I Wilson2, the nucleus that act as a cap of the minus ends. Transport of Cai Lei3, Wanjin Hong3, Diana Murray4, organelles and vesicles along the microtubule network is Roger L Williams2 and Wonhwa Cho1,* driven by two types of motor proteins; dyneins and kinesins (KIF) (Caviston and Holzbaur, 2006). While one major form 1Department of Chemistry, University of Illinois at Chicago, Chicago, IL, USA, 2MRC Laboratory of Molecular Biology, Cambridge, UK, of dynein is known to drive the minus end-directed transport 3Membrane Biology Laboratory, Institute of Molecular and Cell Biology, of many different cargos, KIFs are an extended superfamily of Singapore, Singapore and 4Department of Microbiology and microtubule motor proteins, many of which drive cargos Immunology, Weill Medical College of Cornell University, New York, toward the plus end (Miki et al, 2005; Caviston and NY, USA Holzbaur, 2006). The KIF superfamily is divided into 14 families, classified by KIF16B is a newly identified kinesin that regulates the both structure and function (Miki et al, 2005). All KIFs contain intracellular motility of early endosomes. KIF16B is un- an approximately 360-residue catalytic core domain that is ique among kinesins in that its cargo binding is mediated responsible for microtubule binding and ATP-dependant primarily by the strong interaction of its PX domain with movement along the microtubules. For many KIFs, the con- endosomal lipids. -
Crystal Structure of the PX Domain of SNX27
ISSN 0006-2979, Biochemistry (Moscow), 2019, Vol. 84, No. 2, pp. 147-152. © Pleiades Publishing, Ltd., 2019. Published in Russian in Biokhimiya, 2019, Vol. 84, No. 2, pp. 223-228. Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM18-189, November 19, 2018. Crystal Structure of the PX Domain of SNX27 Y. Li1,a, S. Liao1,b, F. Li1,c, and Z. Zhu1,d* 1Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, 230027 Hefei, China ae-mail: [email protected] be-mail: [email protected] ce-mail: [email protected] de-mail: [email protected] Received July 5, 2018 Revised September 29, 2018 Accepted September 29, 2018 Abstract—SNX27 is a component of the retromer complex essential for the recycling of transmembrane receptors. SNX27 contains the N-terminal Phox (PX) domain that binds inositol 1,3-diphosphate (Ins(1,3)P2) and is important for the SNX27 localization. Here, we determined the crystal structure of human SNX27 PX domain by X-ray crystallography. We found that the sulfate ion is located in the positively charged lipid-binding pocket of the PX domain, which mimics the phospholipid recognition. In addition, we modelled the SNX27-PX–Ins(1,3)P2 complex to better understand the mechanism of Ins(1,3)P2 recognition by the PX domain of SNX27. DOI: 10.1134/S0006297919020056 Keywords: SNX27, lipid binding, PX domain, crystal structure Endocytosis is an energy consuming process that phate (Ins(1,3)P2) [8, 9]. -
SNX13 Reduction Mediates Heart Failure Through Degradative Sorting of Apoptosis Repressor with Caspase Recruitment Domain
ARTICLE Received 2 May 2014 | Accepted 8 Sep 2014 | Published 8 Oct 2014 DOI: 10.1038/ncomms6177 SNX13 reduction mediates heart failure through degradative sorting of apoptosis repressor with caspase recruitment domain Jun Li1,2,*, Changming Li1,3,*, Dasheng Zhang1,2, Dan Shi1,2, Man Qi1,3, Jing Feng1,3, Tianyou Yuan1,2, Xinran Xu1,2, Dandan Liang1,2, Liang Xu1,2, Hong Zhang1,2, Yi Liu1,2, Jinjin Chen1,3, Jiangchuan Ye1,3, Weifang Jiang4, Yingyu Cui1,5, Yangyang Zhang6, Luying Peng1,2,5, Zhaonian Zhou1,7 & Yi-Han Chen1,2,3,5 Heart failure (HF) is associated with complicated molecular remodelling within cardio- myocytes; however, the mechanisms underlying this process remain unclear. Here we show that sorting nexin-13 (SNX13), a member of both the sorting nexin and the regulator of G protein signalling (RGS) protein families, is a potent mediator of HF. Decreased levels of SNX13 are observed in failing hearts of humans and of experimental animals. SNX13-deficient zebrafish recapitulate HF with striking cardiomyocyte apoptosis. Mechanistically, a reduction in SNX13 expression facilitates the degradative sorting of apoptosis repressor with caspase recruitment domain (ARC), which is a multifunctional inhibitor of apoptosis. Consequently, the apoptotic pathway is activated, resulting in the loss of cardiac cells and the dampening of cardiac function. The N-terminal PXA structure of SNX13 is responsible for mediating the endosomal trafficking of ARC. Thus, this study reveals that SNX13 profoundly affects cardiac performance through the SNX13-PXA-ARC-caspase signalling pathway. 1 Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. -
The C2 Domains of the Class I Rab11 Family of Interacting Proteins Target Recycling Vesicles to the Plasma Membrane
Research Article 4365 The C2 domains of the class I Rab11 family of interacting proteins target recycling vesicles to the plasma membrane Andrew J. Lindsay and Mary W. McCaffrey* Molecular Cell Biology Laboratory, Department of Biochemistry, Biosciences Institute, University College Cork, Cork, Ireland *Author for correspondence (e-mail: [email protected]) Accepted 21 April 2004 Journal of Cell Science 117, 4365-4375 Published by The Company of Biologists 2004 doi:10.1242/jcs.01280 Summary The Rab11 family of interacting proteins (Rab11-FIP) is a phosphatidylinositol-(3,4,5)-trisphosphate [PtdIns(3,4,5)P3] recently identified protein family composed of, to date, six and the second messenger phosphatidic acid. Stimulation of members that interact with Rab11. They all share a highly PtdIns(3,4,5)P3 or phosphatidic acid synthesis results in the homologous Rab11-binding domain (RBD) at their C- translocation of the Rab11-FIPs from a perinuclear location termini. However, apart from the RBD, they vary in their to the periphery of the cell. By contrast, the transferrin domain organization. Rab11-FIP3 and Rab11-FIP4 possess receptor does not translocate to the plasma membrane an ezrin-radixin-moesin (ERM) domain in their C-terminal under these conditions. This translocation is dependent on half and EF hands in their N-terminal region. They have the presence of the C2 domain, because class I Rab11-FIP been termed class II Rab11-FIPs. The class I Rab11-FIPs, green-fluorescent-protein fusions that lack the C2 domain Rab coupling protein (RCP), Rip11 and Rab11-FIP2, each cannot translocate to the plasma membrane. -
Solving the FYVE Domain–Ptdins(3)P Puzzle
© 2001 Nature Publishing Group http://structbio.nature.com news and views Solving the FYVE domain–PtdIns(3)P puzzle Paul C. Driscoll Recent crystallographic analyses of membrane-tethering FYVE finger domains from proteins involved in the regulation of endocytic vesicle trafficking have led to conflicting views of the precise nature of the contacts formed with the specific phospholipid ligand. New NMR data obtained for ligand-bound forms of a FYVE domain help resolve the atomic details of this interaction. The truly dynamic nature of eukaryotic cell membranes is brought into sharp focus by the text book description of receptor-mediated endocytosis: ∼50% of the plasma membrane is internalized and recycled every hour whereas the synthesis of new membrane is perhaps one tenth of this rate. The highly regulated process of endocytosis, by which cells recover fluid, chemicals and specific macromolecules from the external environment, is the tar- get of intense investigation. The interplay of cytosolic proteins with constituent plasma and endosomal membranes pro- vides many challenges to structural biolo- gists, not least at the interface between the soluble components and the membrane lipids themselves. Progress by the tradi- tional methods of structural investigation at this ‘phase boundary’ is particularly difficult. © http://structbio.nature.com Group 2001 Nature Publishing In a paper published recently in Science, Kutateladze and Overduin1 report an extension of their earlier work using NMR spectroscopy to analyze the lipid interactions of the FYVE protein domain from the protein early endosome Fig. 1 The chemical structure of PtdIns(3)P and the predicted ‘side-on’ interaction with the FYVE antigen-1 (EEA1).