2axh
Crystal structures of T cell receptor beta chains related to rheumatoid arthritis
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OverviewOverview
The crystal structures of the Vbeta17+ beta chains of two human T cell, receptors (TCRs), originally derived from the synovial fluid (SF4) and, tissue (C5-1) of a patient with rheumatoid arthritis (RA), have been, determined in native (SF4) and mutant (C5-1(F104-->Y/C187-->S)) forms, respectively. These TCR beta chains form homo-dimers in solution and in, crystals. Structural comparison reveals that the main-chain conformations, in the CDR regions of the C5-1 and SF4 Vbeta17 closely resemble those of a, Vbeta17 JM22 in a bound form; however, the CDR3 region shows different, conformations among these three Vbeta17 structures. At the side-chain, level, conformational differences were observed at the CDR2 regions, between our two ligand-free forms and the bound JM22 form. Other, significant differences were observed at the Vbeta regions 8-12, 40-44, and 82-88 between C5-1/SF4 and JM22 Vbeta17, implying that there is, considerable variability in the structures of very similar beta chains., Structural alignments also reveal a considerable variation in the, Vbeta-Cbeta associations, and this may affect ligand recognition. The, crystal structures also provide insights into the structure basis of T, cell recognition of Mycoplasma arthritidis mitogen (MAM), a superantigen, that may be implicated in the development of human RA. Structural, comparisons of the Vbeta domains of known TCR structures indicate that, there are significant similarities among Vbeta regions that are, MAM-reactive, whereas there appear to be significant structural, differences among those Vbeta regions that lack MAM-reactivity. It further, reveals that CDR2 and framework region (FR) 3 are likely to account for, the binding of TCR to MAM.
About this StructureAbout this Structure
2AXH is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of T cell receptor (beta) chains related to rheumatoid arthritis., Li H, Van Vranken S, Zhao Y, Li Z, Guo Y, Eisele L, Li Y, Protein Sci. 2005 Dec;14(12):3025-38. Epub 2005 Oct 31. PMID:16260763
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