Mechanism of chaperonin action: GroES binding and release can drive GroEL-mediated protein folding in the absence of ATP hydrolysis Journal Article
| Authors: | Hayer-Hartl, M. K.; Weber, F.; Hartl, F. U. |
| Article Title: | Mechanism of chaperonin action: GroES binding and release can drive GroEL-mediated protein folding in the absence of ATP hydrolysis |
| Abstract: | As a basic principle, assisted protein folding by GroEL has been proposed to involve the disruption of misfolded protein structures through ATP hydrolysis and interaction with the cofactor GroES. Here, we describe chaperonin subreactions that prompt a re-examination of this view. We find that GroEL-bound substrate polypeptide can induce GroES cycling on and off GroEL in the presence of ADP. This mechanism promotes efficient folding of the model protein rhodanese, although at a slower rate than in the presence of ATP. Folding occurs when GroES displaces the bound protein into the sequestered volume of the GroEL cavity. Resulting native protein leaves GroEL upon GroES release. A single-ring variant of GroEL is also fully functional in supporting this reaction cycle. We conclude that neither the energy of ATP hydrolysis nor the allosteric coupling of the two GroEL rings is directly required for GroEL/GroES-mediated protein folding. The minimal mechanism of the reaction is the binding and release of GroES to a polypeptide-containing ring of GroEL, thereby closing and opening the GroEL folding cage. The role of ATP hydrolysis is mainly to induce conformational changes in GroEL that result in GroES cycling at a physiologically relevant rate. |
| Keywords: | controlled study; protein conformation; animals; models, biological; protein binding; protein interaction; enzyme activation; adenosine diphosphate; escherichia coli; protein secretion; cattle; conformational transition; adenosine triphosphate; protein folding; protein structure; hydrolysis; chromatography, gel; electrophoresis, polyacrylamide gel; allosterism; polypeptide; molecular chaperones; chaperonins; priority journal; article; groel; adenylyl imidodiphosphate; endopeptidase k; chaperonin; groel protein; thiosulfate sulfurtransferase; groes protein; groes |
| Journal Title: | EMBO Journal |
| Volume: | 15 |
| Issue: | 22 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 1996-11-15 |
| Start Page: | 6111 |
| End Page: | 6121 |
| Language: | English |
| PUBMED: | 8947033 |
| PROVIDER: | scopus |
| PMCID: | PMC452432 |
| DOI: | 10.1002/j.1460-2075.1996.tb00999.x |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
