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Crystal structure of ATP-bound Get3-Get4-Get5 complex reveals regulation of Get3 by Get4

Correct localization of membrane proteins is essential to all cells. Chaperone cascades coordinate the capture and handover of substrate proteins from the ribosome to their target membrane; yet the mechanistic and structural details of these processes remain unclear. Here we investigate the conserve...

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Autores principales: Gristick, Harry B., Rao, Meera, Chartron, Justin W., Rome, Michael E., Shan, Shu-ou, Clemons, William M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386898/
https://www.ncbi.nlm.nih.gov/pubmed/24727835
http://dx.doi.org/10.1038/nsmb.2813
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author Gristick, Harry B.
Rao, Meera
Chartron, Justin W.
Rome, Michael E.
Shan, Shu-ou
Clemons, William M.
author_facet Gristick, Harry B.
Rao, Meera
Chartron, Justin W.
Rome, Michael E.
Shan, Shu-ou
Clemons, William M.
author_sort Gristick, Harry B.
collection PubMed
description Correct localization of membrane proteins is essential to all cells. Chaperone cascades coordinate the capture and handover of substrate proteins from the ribosome to their target membrane; yet the mechanistic and structural details of these processes remain unclear. Here we investigate the conserved GET pathway, in which the Get4-Get5 complex mediates the handover of tail-anchor (TA) substrates from the co-chaperone Sgt2 to the Get3 ATPase, the central targeting factor. We present a crystal structure of a yeast Get3-Get4-Get5 complex in an ATP-bound state, and show how Get4 primes Get3 into the optimal configuration for substrate capture. Structure-guided biochemical analyses demonstrate that Get4-mediated regulation of ATP hydrolysis by Get3 is essential to efficient TA protein targeting. Analogous regulation of other chaperones or targeting factors could provide a general mechanism for ensuring effective substrate capture during protein biogenesis.
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spelling pubmed-43868982015-04-06 Crystal structure of ATP-bound Get3-Get4-Get5 complex reveals regulation of Get3 by Get4 Gristick, Harry B. Rao, Meera Chartron, Justin W. Rome, Michael E. Shan, Shu-ou Clemons, William M. Nat Struct Mol Biol Article Correct localization of membrane proteins is essential to all cells. Chaperone cascades coordinate the capture and handover of substrate proteins from the ribosome to their target membrane; yet the mechanistic and structural details of these processes remain unclear. Here we investigate the conserved GET pathway, in which the Get4-Get5 complex mediates the handover of tail-anchor (TA) substrates from the co-chaperone Sgt2 to the Get3 ATPase, the central targeting factor. We present a crystal structure of a yeast Get3-Get4-Get5 complex in an ATP-bound state, and show how Get4 primes Get3 into the optimal configuration for substrate capture. Structure-guided biochemical analyses demonstrate that Get4-mediated regulation of ATP hydrolysis by Get3 is essential to efficient TA protein targeting. Analogous regulation of other chaperones or targeting factors could provide a general mechanism for ensuring effective substrate capture during protein biogenesis. 2014-04-13 2014-05 /pmc/articles/PMC4386898/ /pubmed/24727835 http://dx.doi.org/10.1038/nsmb.2813 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Gristick, Harry B.
Rao, Meera
Chartron, Justin W.
Rome, Michael E.
Shan, Shu-ou
Clemons, William M.
Crystal structure of ATP-bound Get3-Get4-Get5 complex reveals regulation of Get3 by Get4
title Crystal structure of ATP-bound Get3-Get4-Get5 complex reveals regulation of Get3 by Get4
title_full Crystal structure of ATP-bound Get3-Get4-Get5 complex reveals regulation of Get3 by Get4
title_fullStr Crystal structure of ATP-bound Get3-Get4-Get5 complex reveals regulation of Get3 by Get4
title_full_unstemmed Crystal structure of ATP-bound Get3-Get4-Get5 complex reveals regulation of Get3 by Get4
title_short Crystal structure of ATP-bound Get3-Get4-Get5 complex reveals regulation of Get3 by Get4
title_sort crystal structure of atp-bound get3-get4-get5 complex reveals regulation of get3 by get4
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386898/
https://www.ncbi.nlm.nih.gov/pubmed/24727835
http://dx.doi.org/10.1038/nsmb.2813
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