Anna Marie C. Marcelino and Robert G. Smock contributed equally to this work.
1097-0134/asset/PROT_centre.gif?v=1&s=77b56b1f2cdaba74cb3bb149bd9b029cd8803cdb)
Research Article
Evolutionary coupling of structural and functional sequence information in the intracellular lipid-binding protein family †
Article first published online: 13 FEB 2006
DOI: 10.1002/prot.20860
Copyright © 2006 Wiley-Liss, Inc.
Issue
1097-0134/asset/cover.gif?v=1&s=d817e79b67ba6cacf8bdcce1a819c04de300a7e3 "Proteins: Structure, Function, and Bioinformatics")
Proteins: Structure, Function, and Bioinformatics
Special Issue: In honor of George Rose on the occasion of his 65th birthday
Volume 63, Issue 2, pages 373–384, 1 May 2006
Additional Information
How to Cite
Marcelino, A. M. C., Smock, R. G. and Gierasch, L. M. (2006), Evolutionary coupling of structural and functional sequence information in the intracellular lipid-binding protein family . Proteins: Structure, Function, and Bioinformatics, 63: 373–384. doi: 10.1002/prot.20860
- †
This paper is dedicated to George Rose on the occasion of his 65th birthday. We have enjoyed many years of scientific partnership and exchange, which has led to a much valued friendship. Your ability to distill the essence, see what others miss, and explain complex concepts lucidly has inspired our work and that of the field. Many happy (re)-turns, and for that matter helices and sheets, George!
Publication History
- Issue published online: 9 MAR 2006
- Article first published online: 13 FEB 2006
- Manuscript Accepted: 24 OCT 2005
- Manuscript Received: 8 OCT 2005
Funded by
- National Institutes of Health. Grant Number: GM027616
Keywords:
- statistical coupling analysis;
- intracellular lipid-binding proteins;
- protein folding
Abstract
We have mined the evolutionary record for the large family of intracellular lipid-binding proteins (iLBPs) by calculating the statistical coupling of residue variations in a multiple sequence alignment using methods developed by Ranganathan and coworkers (Lockless and Ranganathan, Science 1999:286;295–299). The 213 sequences analyzed have a wide range of ligand-binding functions as well as highly divergent phylogenetic origins, assuring broad sampling of sequence space. Emerging from this analysis were two major clusters of coupled residues, which when mapped onto the structure of a representative iLBP under study in our laboratory, cellular retinoic-acid binding protein I, are largely contiguous and provide useful points of comparison to available data for the folding of this protein. One cluster comprises a predominantly hydrophobic core away from the ligand-binding site and likely represents key structural information for the iLBP fold. The other cluster includes the portal region where ligand enters its binding site, regions of the ligand-binding cavity, and the region where the 10-stranded β-barrel characteristic of this family closes (between strands 1′ and 10). Linkages between these two clusters suggest that evolutionary pressures on this family constrain structural and functional sequence information in an interdependent fashion. The necessity of the structure to wrap around a hydrophobic ligand confounds the typical sequestration of hydrophobic side chains. Additionally, ligand entry and exit require these structures to have a capacity for specific conformational change during binding and release. We conclude that an essential and structurally apparent separation of local and global sequence information is conserved throughout the iLBP family. Proteins 2006. © 2006 Wiley-Liss, Inc.