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


     

Protein Science (2004), 13:608-616. Published by Cold Spring Harbor Laboratory Press. Copyright © 2004 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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Blouin, C.
Right arrow Articles by Roger, A. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Blouin, C.
Right arrow Articles by Roger, A. J.
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?

Rapid evolution in conformational space: A study of loop regions in a ubiquitous GTP binding domain

Christian Blouin1,2, Davin Butt2 and Andrew James Roger1,3

1 Genome Atlantic, Department of Biochemistry and Molecular Biology and
2 Faculty of Computer Science, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1W5
3 Canadian Institute for Advanced Research, Program in Evolutionary Biology, Toronto, Ontario, Canada M5G 1Z8

(RECEIVED July 7, 2003; FINAL REVISION November 7, 2003; ACCEPTED November 7, 2003)



Abstract

The rapidly evolving subsets of a protein are often evident in multiple sequence alignments as poorly defined, gap-containing regions. We investigated the 3D context of these regions observed in 28 protein structures containing a GTP-binding domain assumed to be homologous to the transforming factor p21-RAS. The phylogenetic depth of this data set is such that it is possible to observe lineages sharing a common protein core that diverged early in the eukaryotic cell history. The sequence variability among these homolog proteins is directly linked to the structural variability of surface loops. We demonstrate that these regions are self-contained and thus mostly free of the evolutionary constraints imposed by the conserved core of the domain. These intraloop interactions have the property to create stem-like structures. Interestingly, these stem-like structures can be observed in loops of varying size, up to the size of small protein domains. We propose a model under which the diversity of protein topologies observed in these loops can be the product of a stochastic sampling of sequence and conformational space in a near-neutral fashion, while the proximity of the functional features of the domain core allows novel beneficial traits to be fixed. Our comparative observations, limited here to the proteins containing the RAS-like GTP-binding domain, suggest that a stochastic process of insertion/deletion analogous to "budding" of loops is a likely mechanism of structural innovation. Such a framework could be experimentally exploited to investigate the folding of increasingly complex model inserts.

Keywords: G-protein; evolution; structural alignment; loop; insertion

Reprint requests to: Christian Blouin, Genome Atlantic, Department of Biochemistry and Molecular Biology, Dalhousie University, 6050 University Avenue, Halifax, NS, Canada B3H 1W5; e-mail: cblouin{at}cs.dal.ca; fax: (902) 494-1517.

Supplemental material: See www.proteinscience.org

Article and publication are at http://www.proteinscience.org/cgi/doi/10.1110/ps.03299804.


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?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
P. J. Paukstelis and A. M. Lambowitz
Identification and evolution of fungal mitochondrial tyrosyl-tRNA synthetases with group I intron splicing activity
PNAS, April 22, 2008; 105(16): 6010 - 6015.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
N. Fernandez-Fuentes, B. Oliva, and A. Fiser
A supersecondary structure library and search algorithm for modeling loops in protein structures.
Nucleic Acids Res., January 1, 2006; 34(7): 2085 - 2097.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2004 by The Protein Society.