MBE Advance Access originally published online on January 30, 2007
Molecular Biology and Evolution 2007 24(4):1032-1044; doi:10.1093/molbev/msm022
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research Articles |
Functional Coevolutionary Networks of the Hsp70–Hop–Hsp90 System Revealed through Computational Analyses
* Molecular Evolution and Bioinformatics Laboratory, Department of Biology, National University of Ireland, Maynooth, Ireland
Evolutionary Genetics and Bioinformatics Laboratory, Department of Genetics, Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin, Ireland
E-mail: faresm{at}tcd.ie.
Accepted for publication January 26, 2007.
Currently, the identification of groups of amino acid residues that are important in the function, structure, or interaction of a protein can be both costly and prohibitively complex, involving vast numbers of mutagenesis experiments. Here, we present the application of a novel computational method, which identifies the presence of coevolution in a data set, thereby enabling the a priori identification of amino acid residues that play an important role in protein function. We have applied this method to the heat shock protein (Hsp) protein-folding system, studying the network between Hsp70, Hsp90, and Hop (heat shock–organizing protein). Our analysis has identified functional residues within the tetratricopeptide repeat (TPR) 1 and 2A domains in Hop, previously shown to be interacting with Hsp70 and Hsp90, respectively. Further, we have identified significant residues elsewhere in Hop within domains that have been recently proposed as being important for Hop interaction with Hsp70 and/or Hsp90. In addition, several amino acid sites present in groups of coevolution were identified as 3-dimensionally or linearly proximal to functionally important sites or domains. Based on our results, we also investigate a further functional domain within Hop, between TPR1 and TPR2A, which we suggest as being functionally important in the interaction of Hop with both Hsp70 and Hsp90 whether directly or otherwise. Our method has identified all the previously characterized functionally important regions in this system, thereby indicating the power of this method in the a priori identification of important regions for site-directed mutagenesis studies
Key Words: Hsp90 • Hop • Hsp70 • functional coevolution
Michele Vendruscolo, Associate Editor
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. F. Smith and D. O. Toft Minireview: The Intersection of Steroid Receptors with Molecular Chaperones: Observations and Questions Mol. Endocrinol., October 1, 2008; 22(10): 2229 - 2240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. A. Travers, D. C. Tully, G. P. McCormack, and M. A. Fares A Study of the Coevolutionary Patterns Operating within the env Gene of the HIV-1 Group M Subtypes Mol. Biol. Evol., December 1, 2007; 24(12): 2787 - 2801. [Abstract] [Full Text] [PDF]
|
|