Affiliations: Department of Medicine, Manipal University, Manipal
576 104, Karnataka, India | National Centre for Biological Sciences (TIFR),
Bangalore 560 065, India
Note: [] Corresponding author. Ramanathan Sowdhamini, National Centre for
Biological Sciences (TIFR), GKVK Campus, Bellary Road, Bangalore 560 065,
India. Tel.: +91 80 23666250; Fax: +91 80 23636462; E-mail: mini@ncbs.res.in
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 β_{1}-β_{2}
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.
