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Title: Structure of the Get3 targeting factor in complex with its membrane protein cargo

Abstract

How to GET to the right membrane Membrane proteins with a hydrophobic transmembrane domain (TMD) play critical roles in virtually all aspects of cell physiology. After it has been synthesized in the cytosol, this TMD must be targeted to and inserted into the correct membrane. The GET pathway is one of two targeting pathways to the endoplasmic reticulum conserved across all eukaryotes. It is not clear how the central targeting factor, Get3, recognizes a TMD to shield it from aggregation until it is successfully inserted into the membrane. Now, Mateja et al. show that the functional targeting complex comprises a Get3 dimer bound to a single TMD. The helical hydrophobic TMD binds deep within a large hydrophobic groove in the Get3 dimer. This groove closes slightly upon TMD binding, forming a dynamic “lid” over the mouth of the groove. Science , this issue p. 1152

Authors:
 [1];  [1];  [1];  [1];  [1];  [2];  [1]
  1. Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
  2. MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Publication Date:
Research Org.:
Univ. of Chicago, IL (United States); MRC Lab. of Molecular Biology, Cambridge (United Kingdom)
Sponsoring Org.:
USDOE; National Inst. of Health (NIH) (United States); Medical Research Council (MRC) (United Kingdom)
OSTI Identifier:
1353292
Alternate Identifier(s):
OSTI ID: 1172425
Grant/Contract Number:  
AC02-06CH11357; P41 GM103403; MC_UP_A022_1007; U01 GM094588; U54 GM087519; R01 GM086487
Resource Type:
Published Article
Journal Name:
Science
Additional Journal Information:
Journal Name: Science Journal Volume: 347 Journal Issue: 6226; Journal ID: ISSN 0036-8075
Publisher:
American Association for the Advancement of Science (AAAS)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Mateja, Agnieszka, Paduch, Marcin, Chang, Hsin-Yang, Szydlowska, Anna, Kossiakoff, Anthony A., Hegde, Ramanujan S., and Keenan, Robert J. Structure of the Get3 targeting factor in complex with its membrane protein cargo. United States: N. p., 2015. Web. doi:10.1126/science.1261671.
Mateja, Agnieszka, Paduch, Marcin, Chang, Hsin-Yang, Szydlowska, Anna, Kossiakoff, Anthony A., Hegde, Ramanujan S., & Keenan, Robert J. Structure of the Get3 targeting factor in complex with its membrane protein cargo. United States. https://doi.org/10.1126/science.1261671
Mateja, Agnieszka, Paduch, Marcin, Chang, Hsin-Yang, Szydlowska, Anna, Kossiakoff, Anthony A., Hegde, Ramanujan S., and Keenan, Robert J. Fri . "Structure of the Get3 targeting factor in complex with its membrane protein cargo". United States. https://doi.org/10.1126/science.1261671.
@article{osti_1353292,
title = {Structure of the Get3 targeting factor in complex with its membrane protein cargo},
author = {Mateja, Agnieszka and Paduch, Marcin and Chang, Hsin-Yang and Szydlowska, Anna and Kossiakoff, Anthony A. and Hegde, Ramanujan S. and Keenan, Robert J.},
abstractNote = {How to GET to the right membrane Membrane proteins with a hydrophobic transmembrane domain (TMD) play critical roles in virtually all aspects of cell physiology. After it has been synthesized in the cytosol, this TMD must be targeted to and inserted into the correct membrane. The GET pathway is one of two targeting pathways to the endoplasmic reticulum conserved across all eukaryotes. It is not clear how the central targeting factor, Get3, recognizes a TMD to shield it from aggregation until it is successfully inserted into the membrane. Now, Mateja et al. show that the functional targeting complex comprises a Get3 dimer bound to a single TMD. The helical hydrophobic TMD binds deep within a large hydrophobic groove in the Get3 dimer. This groove closes slightly upon TMD binding, forming a dynamic “lid” over the mouth of the groove. Science , this issue p. 1152},
doi = {10.1126/science.1261671},
journal = {Science},
number = 6226,
volume = 347,
place = {United States},
year = {Fri Mar 06 00:00:00 EST 2015},
month = {Fri Mar 06 00:00:00 EST 2015}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1126/science.1261671

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Cited by: 83 works
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