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

Abstract

Fifty-two 3D structures of Ig-like domains covering the immunoglobulin fold family (IgFF) were compared and classified according to the conservation of their secondary structures. Members of the IgFF are distantly related proteins or evolutionarily unrelated proteins with a similar fold, the Ig fold. In this paper, a multiple structural alignment of the conserved common core is described and the correlation between corresponding sequences is discussed. While the members of the IgFF exhibit wide heterogeneity in terms of tissue and species distribution or functional implications, the 3D structures of these domains are far more conserved than their sequences. We define topologically equivalent residues in the Ig-like domains, describe the hydrophobic common cores and discuss the presence of additional strands. The disulfide bridges, not necessary for the stability of the Ig fold, may have an effect on the compactness of the domains. Based upon sequence and structure analysis, we propose the introduction of two new subtypes (C3 and C4) to the previous classifications, in addition to a new global structural classification. The very low mean sequence identity between subgroups of the IgFF suggests the occurrence of both divergent and convergent evolutionary processes, explaining the wide diversity of the superfamily. Finally, this review suggest that hydrophobic residues constituting the common hydrophobic cores are important clues to explain how highly divergent sequences can adopt a similar fold.

Structural basis of mouse cytomegalovirus m152/gp40 interaction with RAE1γ reveals a paradigm for MHC/MHC interaction in immune evasion

“…S1) the α3 domain lacks the intradomain disulfide joining Cys197 to Cys248 found in most other MHC-Iv proteins. This domain is characterized by a novel eight-stranded variation on the seven-stranded C1-type Ig-fold (24), adding a β0 strand from the amino terminus to the three-stranded sheet (Fig. 1B and Fig.…”

Structure of the Globular Tail of Nuclear Lamin

“…Ig-like domains have been further categorized into four groups according to the presence of ancillary ␤ strands and the connections between them (Fig. 2b) (25,26). Because it is different from the previously defined subtypes, the lamin A/C tail represents the prototype for a new class of Ig-related domain, which we refer to as the lamin or L subtype.…”

“…Although different classes within the Ig domain family share very low (Ͻ10%) sequence identity, certain residues that contribute to the domain core have conserved function. Residue c3 (third position in ␤ strand c) is invariably hydrophobic, while residues a3, b1, e5, and f5 are hydrophobic in most cases (26). All of these residues in lamin A/C are hydrophobic: c3 ϭ Ile 469 ; a3 ϭ Val 442 ; b1 ϭ Phe 451 ; e5 ϭ Ile 497 ; f5 ϭ Leu 530 .…”

The descent of the antibody-based immune system by gradual evolution

“…These domains, which can be distinguished into seven main types (V, C1, C2, C3, C4, I, and FnIII) (39), all share the basic Ig-fold structure consisting of two ␤-pleated sheets of a sandwich rolled into a cylinder (Fig. 1).…”