Unknown

Dataset Information

0

The charged linker of the molecular chaperone Hsp90 modulates domain contacts and biological function.


ABSTRACT: The heat shock protein 90 (Hsp90) is a dimeric molecular chaperone essential in numerous cellular processes. Its three domains (N, M, and C) are connected via linkers that allow the rearrangement of domains during Hsp90's chaperone cycle. A unique linker, called charged linker (CL), connects the N- and M-domain of Hsp90. We used an integrated approach, combining single-molecule techniques and biochemical and in vivo methods, to study the unresolved structure and function of this region. Here we show that the CL facilitates intramolecular rearrangements on the milliseconds timescale between a state in which the N-domain is docked to the M-domain and a state in which the N-domain is more flexible. The docked conformation is stabilized by 1.1 kBT (2.7 kJ/mol) through binding of the CL to the N-domain of Hsp90. Docking and undocking of the CL affects the much slower intermolecular domain movement and Hsp90's chaperone cycle governing client activation, cell viability, and stress tolerance.

SUBMITTER: Jahn M 

PROVIDER: S-EPMC4273377 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

The charged linker of the molecular chaperone Hsp90 modulates domain contacts and biological function.

Jahn Markus M   Rehn Alexandra A   Pelz Benjamin B   Hellenkamp Björn B   Richter Klaus K   Rief Matthias M   Buchner Johannes J   Hugel Thorsten T  

Proceedings of the National Academy of Sciences of the United States of America 20141202 50


The heat shock protein 90 (Hsp90) is a dimeric molecular chaperone essential in numerous cellular processes. Its three domains (N, M, and C) are connected via linkers that allow the rearrangement of domains during Hsp90's chaperone cycle. A unique linker, called charged linker (CL), connects the N- and M-domain of Hsp90. We used an integrated approach, combining single-molecule techniques and biochemical and in vivo methods, to study the unresolved structure and function of this region. Here we  ...[more]

Shared Molecules

Only show the datasets with similarity scores above: 0.5
     

Similar Datasets

| S-EPMC3287002 | biostudies-literature
| S-EPMC8048802 | biostudies-literature
| S-EPMC8459299 | biostudies-literature
| S-EPMC3282117 | biostudies-literature
| S-EPMC3739785 | biostudies-literature
| S-EPMC1839984 | biostudies-literature
| S-EPMC6248305 | biostudies-literature
| S-EPMC8304327 | biostudies-literature
| S-EPMC5070531 | biostudies-literature
| S-EPMC2781518 | biostudies-literature