Sequence and structural analyses of interleukin-8-like chemokine superfamily.
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 beta1-beta2 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.
Kanagarajadurai
Karuppiah
K
Department of Molecular Medicine, Manipal University, Manipal, Karnataka, India.
Sowdhamini
Ramanathan
R
D000595:Amino Acid Sequence; D000818:Animals; D019743:Chemokines, CXC / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D016209:Interleukin-8 / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D019743:Chemokines, CXC; D016209:Interleukin-8