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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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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. |
format | Online Article Text |
id | pubmed-4386898 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
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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