1w0v
CRYSTAL STRUCTURE OF HLA-B*2705 COMPLEXED WITH THE SELF-PEPTIDE TIS FROM EGF-RESPONSE FACTOR 1
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OverviewOverview
The F pocket of major histocompatibility complex (in humans HLA) class I, molecules accommodates the C terminus of the bound peptide. Residues, forming this pocket exhibit considerable polymorphism, and a single, difference (Asp116 in HLA-B*2705 and His116 in HLA-B*2709 heavy chains), confers differential association of these two HLA-B27 subtypes to the, autoimmune disease ankylosing spondylitis. As peptide presentation by HLA, molecules is of central importance for immune responses, we performed, thermodynamic (circular dichroism, differential scanning calorimetry, fluorescence polarization) and X-ray crystallographic analyses of both, HLA-B27 subtypes complexed with the epidermal growth factor response, factor 1-derived self-peptide TIS (RRLPIFSRL) to understand the impact of, the Asp116His exchange on peptide display. This peptide is known to be, presented in vivo by both subtypes, and as expected for a self-peptide, TIS-reactive cytotoxic T lymphocytes are absent in the respective, individuals. The thermodynamic analyses reveal that both HLA-B27:TIS, complexes exhibit comparable, relatively high thermostability (Tm, approximately 60 degrees C) and undergo multi-step unfolding reactions, with dissociation of the peptide in the first step. As shown by X-ray, crystallography, only subtle structural differences between the subtypes, were observed regarding the architecture of their F pockets, including the, presence of distinct networks of water molecules. However, no consistent, structural differences were found between the peptide presentation modes., In contrast to other peptides displayed by the two HLA-subtypes which show, either structural or dynamical differences in their peptide presentation, modes, the TIS-complexed HLA-B*2705 and HLA-B*2709 subtypes are an example, for thermodynamic and structural equivalence, in agreement with functional, data.
DiseaseDisease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142830], Hypoproteinemia, hypercatabolic OMIM:[109700], Spondyloarthropathy, susceptibility to, 1 OMIM:[142830], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[142830]
About this StructureAbout this Structure
1W0V is a Protein complex structure of sequences from Homo sapiens with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Thermodynamic and structural equivalence of two HLA-B27 subtypes complexed with a self-peptide., Hulsmeyer M, Welfle K, Pohlmann T, Misselwitz R, Alexiev U, Welfle H, Saenger W, Uchanska-Ziegler B, Ziegler A, J Mol Biol. 2005 Mar 11;346(5):1367-79. Epub 2005 Jan 28. PMID:15713487
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