Regulation of the Native Protein Landscape in the Nucleus by Molecular Chaperones

NIH RePORTER · NIH · R35 · $376,865 · view on reporter.nih.gov ↗

Abstract

ABSTRACT Homeostasis requires most, if not all, pathways to function rapidly and precisely. While cooperative interactions between proteins and cofactors helps ensure selectivity, the events mediating dynamic action are less well understood. Further complicating pathway performance is the nature of the cell interior, as it is densely packed and often contains multiple binding partners for each protein—both features increase non-productive or off-pathway interactions. These variables present great challenges for achieving homeostasis especially in the midst of fluctuating internal and external stimuli that must be monitored constantly to appropriately initiate, continue, or halt cellular processes. Hence, biological complexes must be actively and persistently disassembled in order to work on a useful time scale. We suggest that the broad binding specificity and energy-independent molecular chaperone activities of the Hsp90 chaperone system govern the kinetic behaviors of the diverse proteins within cells. Basically, Hsp90 and its cochaperones resolve inherently stable cooperative complexes into a dynamic machinery capable of rapid action that enables efficient and timely biological pathways.

Key facts

NIH application ID
10244899
Project number
5R35GM136660-02
Recipient
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
Principal Investigator
Brian C Freeman
Activity code
R35
Funding institute
NIH
Fiscal year
2021
Award amount
$376,865
Award type
5
Project period
2020-09-01 → 2025-06-30