Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
J Mol Biol. 2010 Sep 3;401(5):931-9. doi: 10.1016/j.jmb.2010.06.066. Epub 2010 Jul 6.

Charge-rich regions modulate the anti-aggregation activity of Hsp90.

Author information

  • 1Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, LRB922, 364 Plantation Street, Worcester, MA 01605, USA.

Abstract

Protein aggregation can have dramatic effects on cellular function and plays a causative role in many human diseases. In all cells, molecular chaperones bind to aggregation-prone proteins and hinder aggregation. The ability of a protein to resist aggregation and remain soluble in aqueous solution is linked to the physical properties of the protein. Numerous physical studies demonstrate that charged atoms favor solubility. We note that many molecular chaperones possess a substantial negative charge that may allow them to impart solubility on aggregation-prone proteins. Hsp90 is one such negatively charged molecular chaperone. The charge on Hsp90 is largely concentrated in two highly acidic regions. To investigate the relationship between chaperone charge and protein solubility, we deleted these charge-rich regions and analyzed the resulting Hsp90 constructs for anti-aggregation activity. We found that deletion of both charge-rich regions dramatically impaired Hsp90 anti-aggregation activity. The anti-aggregation role of the deleted charge-rich regions could be due to net charge or sequence-specific features. To distinguish these possibilities, we attached an acid-rich region with a distinct amino acid sequence to our double-deleted Hsp90 construct. This charge rescue construct displayed effective anti-aggregation activity indicating that the net charge of Hsp90 contributes to its anti-aggregation activity.

Copyright (c) 2010 Elsevier Ltd. All rights reserved.

PMID:
20615417
[PubMed - indexed for MEDLINE]
PMCID:
PMC2929759
Free PMC Article

Images from this publication.See all images (5)Free text

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk