Conservation of cys-cys trp structural triads and their geometry in the protein domains of immunoglobulin superfamily members.
In almost all members of the immunoglobulin superfamily (IgSF) for which an experimental structure has been determined, a triad (C-CW) consisting of two cysteine residues that form a disulfide bond and a neighboring tryptophan can be found in the core of the protein fold. We analyzed the geometry of these C-CW triads among a database of 60 Fab crystal structures and found it to be remarkably conserved. We identified C-CW triads of a similar configuration in other members of the IgSF such as T cell receptor (TCR), major histocompatibility complex antigens (MHC), cell surface antigens CD4 and CD8, and cell-adhesion molecules. We used this C-CW pattern to search a database of non-IgSF proteins, and identified several proteins that contain a disulfide bridge associated with a tryptophan in a similar configuration. Examination of the distances and orientations between triads found in adjacent domains in Fab fragments and TCR also reveal a high degree of conservation, which reflects the invariance of the inter-chain domain packing. This high degree of conservation of the geometry of the C-CW triad in IgSF structures suggests that the Trp may contribute significantly to the stability of the disulfide bond. Knowledge of these geometric parameters may prove useful in the construction and validation of theoretical models of Ig, TCR, and other IgSF members.
Ioerger
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Department of Computer Science, Texas A&M University, College Station 77843, USA. ioerger@cs.tamu.edu
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D000818:Animals; D017124:Conserved Sequence; D003545:Cysteine / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007136:Immunoglobulins / Q000737:chemistry*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008565:Membrane Proteins / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry; D014364:Tryptophan / Q000737:chemistry
D004220:Disulfides; C112314:IGSF1 protein, human; D007140:Immunoglobulin Fab Fragments; D007136:Immunoglobulins; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D014364:Tryptophan; D003545:Cysteine