The immunoglobulin fold family: sequence analysis and 3D structure comparisons

Fifty-two 3D structures of Ig-like domains covering the immunoglobulin fold family (IgFF) were compared and classified according to the conservation o f their secondary structures. Members of the IgFF are distantly related pro teins or evolutionarily unrelated proteins with a similar fold, the Ig fold . In this paper, a multiple structural alignment of the conserved common co re is described and the correlation between corresponding sequences is disc ussed. While the members of the IgFF exhibit wide heterogeneity in terms of tissue and species distribution or functional implications, the 3D structu res of these domains are far more conserved than their sequences. We define topologically equivalent residues in the Ig-like domains, describe the hyd rophobic common cores and discuss the presence of additional strands. The d isulfide bridges, not necessary for the stability of the Ig fold, may have an effect on the compactness of the domains. Based upon sequence and struct ure analysis, we propose the introduction of two new subtypes (C3 and C4) t o the previous classifications, in addition to a new global structural clas sification. The very low mean sequence identity between subgroups of the Ig FF suggests the occurrence of both divergent and convergent evolutionary pr ocesses, explaining the wide diversity of the superfamily, Finally, this re view suggest that hydrophobic residues constituting the common hydrophobic cores are important dues to explain how highly divergent sequences can adop t a similar fold.