- Article -
| In Silico Biology 8, 0025 (2008); ©2008, Bioinformation Systems e.V. |
Sequence and structural analyses of interleukin-8-like chemokine superfamily
Karuppiah Kanagarajadurai1, 2 and Ramanathan Sowdhamini2*
1 Department of Molecular Medicine, Manipal University, Manipal 576 104, Karnataka, India
2 National Centre for Biological Sciences (TIFR), GKVK Campus, Bellary Road, Bangalore 560 065, India
* Corresponding author
Email: mailto:mini@ncbs.res.in
Edited by E. Wingender; received February 03, 2008; revised May 16, 2008; accepted May 17, 2008; published August 17, 2008
Abstract
Interleukin-8 and related chemokines are small proteins that bind to receptors belonging to the large family of G-protein-coupled receptors. They can cause migration of cells like neutrophils and eosinophils and some of them are implicated in angiogenic diseases. More than 40 subfamilies of these ligands are known that share poor sequence similarity and display receptor specificity. There is very little structural information about the mode of binding between ligands and the receptors. We have employed multi-fold sensitive sequence search methods to provide a repertoire of 252 putative interleukin-8 proteins and homologues, which are shared across humans, aves and fish. The sequences can be organized into five major known clusters. The propensity of occurrence of certain amino acid alphabets is found to be specific in different locations of the polypeptide fold. The sequence dispersion is also observed to be cluster-specific when examined by Evolutionary Trace procedure. Amino acid alphabet analysis and Evolutionary Trace procedure reveal cluster-specific amino acid distribution that provide clues about how the small fold of the ligand could display remarkable receptor specificity. We notice regions, like the β1-β2 loop of the fold, that are potentially involved in receptor recognition and specificity that could be potential sites for residue mutations. Systematic studies of the distribution patterns enable better understanding of the evolution and molecular recognition of this important and diverse protein superfamily.
Keywords: GPCR superfamily, clustering by phylogeny, structure-function relationship