Display Settings:

Format

Send to:

Choose Destination
Biophys J. 2012 Jun 20;102(12):2828-34. doi: 10.1016/j.bpj.2012.05.006. Epub 2012 Jun 19.

Comparing the folding and misfolding energy landscapes of phosphoglycerate kinase.

Author information

  • 1Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary.

Abstract

Partitioning of polypeptides between protein folding and amyloid formation is of outstanding pathophysiological importance. Using yeast phosphoglycerate kinase as model, here we identify the features of the energy landscape that decide the fate of the protein: folding or amyloidogenesis. Structure formation was initiated from the acid-unfolded state, and monitored by fluorescence from 10 ms to 20 days. Solvent conditions were gradually shifted between folding and amyloidogenesis, and the properties of the energy landscape governing structure formation were reconstructed. A gradual transition of the energy landscape between folding and amyloid formation was observed. In the early steps of both folding and misfolding, the protein searches through a hierarchically structured energy landscape to form a molten globule in a few seconds. Depending on the conditions, this intermediate either folds to the native state in a few minutes, or forms amyloid fibers in several days. As conditions are changed from folding to misfolding, the barrier separating the molten globule and native states increases, although the barrier to the amyloid does not change. In the meantime, the native state also becomes more unstable and the amyloid more stable. We conclude that the lower region of the energy landscape determines the final protein structure.

Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

PMID:
22735533
[PubMed - indexed for MEDLINE]
PMCID:
PMC3379013
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
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