Skip Navigation



PEDS Advance Access published online on April 27, 2005
Protein Engineering Design and Selection, doi:10.1093/protein/gzi025
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary data
Right arrow All Versions of this Article:
18/5/229    most recent
gzi025v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Went, H. M.
Right arrow Articles by Jackson, S. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Went, H. M.
Right arrow Articles by Jackson, S. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oupjournals.org
Received February 11, 2005
Accepted March 22, 2005

Article

Ubiquitin folds through a highly polarized transition state

Heather M. Went 1 and Sophie E. Jackson 1*

1 Chemistry Department and Centre for Protein Engineering, Lensfield Road, Cambridge CB2 1EW, UK

* To whom correspondence should be addressed.
Sophie E. Jackson, E-mail: sej13{at}cam.ac.uk


  Abstract

The small {alpha}/{beta} protein ubiquitin has been used as a model system for experimental and computational studies on protein folding for many years. Here, we present a comprehensive {phi}-value analysis and characterize the structure and energetics of the transition state ensemble (TSE). Twenty-seven non-disruptive mutations are made throughout the structure and a range of {phi}-values from zero to one are observed. The values cluster such that medium and high values and found only in the N-terminal region of the protein, whilst the C-terminal region has consistently low {phi}-values. In the TSE, the main {alpha}-helix appears to be fully formed (two {phi}-values which specifically probe helical structure are one) and the helix is stabilized by packing against the first {beta}-turn, which is partially structured. In striking comparison, the {phi}-values in the C-terminal region are all very low, suggesting that this region of the protein is largely unstructured in the TSE. Data are consistent with a nucleation-condensation mechanism in which there is a highly polarized folding nucleus comprising the first {beta}-hairpin and the {alpha}-helix. Data presented from the protein engineering study and {phi}-value analysis are compared with results from other experimental studies and also computational studies.

Keywords: folding nucleus; nucleation-condensation; transition-state ensemble; two-state.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
H. S. Chung, Z. Ganim, K. C. Jones, and A. Tokmakoff
Multidimensional Ultrafast Spectroscopy Special Feature: Transient 2D IR spectroscopy of ubiquitin unfolding dynamics
PNAS, September 4, 2007; 104(36): 14237 - 14242.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.