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Procollagen Triple Helix Assembly: An Unconventional Chaperone-Assisted Folding Paradigm
Fibers composed of type I collagen triple helices form the organic scaffold of bone and many other tissues, yet the energetically preferred conformation of type I collagen at body temperature is a random coil. In fibers, the triple helix is stabilized by neighbors, but how does it fold? The observat...
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2000351/ https://www.ncbi.nlm.nih.gov/pubmed/17925877 http://dx.doi.org/10.1371/journal.pone.0001029 |
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author | Makareeva, Elena Leikin, Sergey |
author_facet | Makareeva, Elena Leikin, Sergey |
author_sort | Makareeva, Elena |
collection | PubMed |
description | Fibers composed of type I collagen triple helices form the organic scaffold of bone and many other tissues, yet the energetically preferred conformation of type I collagen at body temperature is a random coil. In fibers, the triple helix is stabilized by neighbors, but how does it fold? The observations reported here reveal surprising features that may represent a new paradigm for folding of marginally stable proteins. We find that human procollagen triple helix spontaneously folds into its native conformation at 30–34°C but not at higher temperatures, even in an environment emulating Endoplasmic Reticulum (ER). ER-like molecular crowding by nonspecific proteins does not affect triple helix folding or aggregation of unfolded chains. Common ER chaperones may prevent aggregation and misfolding of procollagen C-propeptide in their traditional role of binding unfolded polypeptide chains. However, such binding only further destabilizes the triple helix. We argue that folding of the triple helix requires stabilization by preferential binding of chaperones to its folded, native conformation. Based on the triple helix folding temperature measured here and published binding constants, we deduce that HSP47 is likely to do just that. It takes over 20 HSP47 molecules to stabilize a single triple helix at body temperature. The required 50–200 µM concentration of free HSP47 is not unusual for heat-shock chaperones in ER, but it is 100 times higher than used in reported in vitro experiments, which did not reveal such stabilization. |
format | Text |
id | pubmed-2000351 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-20003512007-10-10 Procollagen Triple Helix Assembly: An Unconventional Chaperone-Assisted Folding Paradigm Makareeva, Elena Leikin, Sergey PLoS One Research Article Fibers composed of type I collagen triple helices form the organic scaffold of bone and many other tissues, yet the energetically preferred conformation of type I collagen at body temperature is a random coil. In fibers, the triple helix is stabilized by neighbors, but how does it fold? The observations reported here reveal surprising features that may represent a new paradigm for folding of marginally stable proteins. We find that human procollagen triple helix spontaneously folds into its native conformation at 30–34°C but not at higher temperatures, even in an environment emulating Endoplasmic Reticulum (ER). ER-like molecular crowding by nonspecific proteins does not affect triple helix folding or aggregation of unfolded chains. Common ER chaperones may prevent aggregation and misfolding of procollagen C-propeptide in their traditional role of binding unfolded polypeptide chains. However, such binding only further destabilizes the triple helix. We argue that folding of the triple helix requires stabilization by preferential binding of chaperones to its folded, native conformation. Based on the triple helix folding temperature measured here and published binding constants, we deduce that HSP47 is likely to do just that. It takes over 20 HSP47 molecules to stabilize a single triple helix at body temperature. The required 50–200 µM concentration of free HSP47 is not unusual for heat-shock chaperones in ER, but it is 100 times higher than used in reported in vitro experiments, which did not reveal such stabilization. Public Library of Science 2007-10-10 /pmc/articles/PMC2000351/ /pubmed/17925877 http://dx.doi.org/10.1371/journal.pone.0001029 Text en Makareeva et al. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Makareeva, Elena Leikin, Sergey Procollagen Triple Helix Assembly: An Unconventional Chaperone-Assisted Folding Paradigm |
title | Procollagen Triple Helix Assembly: An Unconventional Chaperone-Assisted Folding Paradigm |
title_full | Procollagen Triple Helix Assembly: An Unconventional Chaperone-Assisted Folding Paradigm |
title_fullStr | Procollagen Triple Helix Assembly: An Unconventional Chaperone-Assisted Folding Paradigm |
title_full_unstemmed | Procollagen Triple Helix Assembly: An Unconventional Chaperone-Assisted Folding Paradigm |
title_short | Procollagen Triple Helix Assembly: An Unconventional Chaperone-Assisted Folding Paradigm |
title_sort | procollagen triple helix assembly: an unconventional chaperone-assisted folding paradigm |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2000351/ https://www.ncbi.nlm.nih.gov/pubmed/17925877 http://dx.doi.org/10.1371/journal.pone.0001029 |
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