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

Mateja, Agnieszka; Paduch, Marcin; Chang, Hsin-Yang; Szydlowska, Anna; Kossiakoff, Anthony A.; Hegde, Ramanujan S.; Keenan, Robert J.

doi:10.1126/science.1261671

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

Journal Article · Fri Mar 06 00:00:00 EST 2015 · Science

DOI:https://doi.org/10.1126/science.1261671· OSTI ID:1353292

Mateja, Agnieszka ^[1]; Paduch, Marcin ^[1]; Chang, Hsin-Yang ^[1]; Szydlowska, Anna ^[1]; Kossiakoff, Anthony A. ^[1]; Hegde, Ramanujan S. ^[2]; Keenan, Robert J. ^[1]

Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.

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

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Research Organization:: Univ. of Chicago, IL (United States); MRC Lab. of Molecular Biology, Cambridge (United Kingdom)

Sponsoring Organization:: USDOE; National Inst. of Health (NIH) (United States); Medical Research Council (MRC) (United Kingdom)

Grant/Contract Number:: AC02-06CH11357; P41 GM103403; MC_UP_A022_1007; U01 GM094588; U54 GM087519; R01 GM086487

OSTI ID:: 1353292

Alternate ID(s):: OSTI ID: 1172425

Journal Information:: Science, Journal Name: Science Vol. 347 Journal Issue: 6226; ISSN 0036-8075

Publisher:: American Association for the Advancement of Science (AAAS)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 83 works

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