Sequence profiles of immunoglobulin and immunoglobulin-like domains.
Immunoglobulins (Ig) are highly modular proteins, consisting of variable and constant domains, which have clear, conserved sequence patterns. These sequence patterns have allowed T-cell receptor (TCR) and major histocompatibility complex (MHC) molecule domains, as well as some cell adhesion, cell surface receptor and muscle protein domains, to be identified as forming a superfamily of related proteins together with the Ig-domains. The domains of these proteins have been grouped into four sets: variable (V-set), constant-1 (C1-set), constant-2 (C2-set) and intermediate (I-set). X-ray and NMR studies have shown that these domains form a Greek-key beta-sandwich structure with the sets differing in the number of strands in the beta-sheets as well as in their sequence patterns. The conserved sequence elements in the major sets of Ig and Ig-like molecules have previously been reported as general sequence profiles. This work examines the variability within these sets. Detailed sequence profiles and consensus sequences for these sets and groups have been constructed and a novel form of presentation has been developed to overcome some of the drawbacks of current methods of presenting consensus sequences. The profiles that were constructed allow a comparison of the similarities and differences among the sets of Ig and Ig-like sequences and provide a means by which sequences can be tested for compatibility with Ig-like sequence motifs. As well, the sequence separations of the main residues in the characteristic "pin" structure of Ig-like molecules were examined for variation among the groups. From the profiles constructed here, measures of the degree of conservation within the groups of molecules were determined. These measures were used to assist in a reconsideration of possible evolutionary pathways between the major structural groups of the Ig-superfamily.
Smith
D K
DK
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
Xue
H
H
D000595:Amino Acid Sequence; D017124:Conserved Sequence; D003545:Cysteine; D016208:Databases, Factual; D019143:Evolution, Molecular; D007136:Immunoglobulins / Q000737:chemistry* / Q000378:metabolism; D008285:Major Histocompatibility Complex; D008956:Models, Chemical; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry; D016415:Sequence Alignment
D007136:Immunoglobulins; D011948:Receptors, Antigen, T-Cell; D003545:Cysteine