Protein Science
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Protein Science (2007), 16:744-754. Published by Cold Spring Harbor Laboratory Press. Copyright © 2007 The Protein Society
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Research Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wetzler, D. E.
Right arrow Articles by de Prat-Gay, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wetzler, D. E.
Right arrow Articles by de Prat-Gay, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

A quasi-spontaneous amyloid route in a DNA binding gene regulatory domain: The papillomavirus HPV16 E2 protein

Diana E. Wetzler, Eduardo M. Castaño, and Gonzalo de Prat-Gay

Instituto Leloir and CONICET, Buenos Aires 1405, Argentina

(RECEIVED October 3, 2006; FINAL REVISION November 29, 2006; ACCEPTED December 22, 2006)

The DNA binding domain of papillomavirus E2 proteins is at the center of the regulation of gene transcription and replication of the virus. Its unique fold consists of a beta-barrel domain that combines an eight-stranded dimeric beta-barrel core interface with two symmetrical DNA binding {alpha}-helices and other two helices, packed against the central barrel. Treatment with low amounts of trifluoroethanol readily leads to a mostly beta-sheet oligomeric species, with a loss of near-UV circular dichroism signal and increase in its ANS binding capacity, indicating that buried hydrophobic surfaces become accessible to the solvent. This species subsequently undergoes a slow transition into amyloid aggregates as determined by light scattering and Congo red and thioflavin T binding. Electron microscopy shows short amyloid fibers with a curly aspect as the end product. The amyloid route is completely prevented by addition of stoichiometrical amounts of specific DNA, strongly suggesting that unfolding of the DNA binding {alpha}-helix is required for the formation of the intermediate. The slow nature of this expanded beta-oligomeric species and the availability of several different conformational probes make it an excellent model for investigating amyloid mechanisms. The mild perturbation required for entering an amyloid route is indicative of a preexisting equilibrium. Oligomerization processes are required for the assembly of transcription initiation and DNA replication machineries, where proteins from different viruses must come together with host cell proteins. The E2 protein is a virus-encoded multifunctional master regulator that may exert one of its multiple functions through its ability to oligomerize.

Keywords: DNA binding domains; protein structure/folding; circular dichroism; fluorescence; kinetics; amyloid; beta-oligomers; E2 protein; HPV


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by The Protein Society.