5deg

Crystal structure of B*27:06 bound to the pVIPR peptide

spinqualitylabelsall models 5deg, resolution 1.83Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5deg is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL Related: 1of2, 1ogt Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Disease [B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:241600]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation. Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis. Function [Q7YQB0_HUMAN] Involved in the presentation of foreign antigens to the immune system.[SAAS:SAAS00281819] [B2MG_HUMAN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Publication Abstract from PubMed OBJECTIVE: Dissimilarities in antigen processing and presentation are known to contribute to the differential association of HLA-B*27 subtypes with the inflammatory rheumatic disease ankylosing spondylitis (AS). In support of this contention, previous X-ray crystallographic data showed that peptides can be displayed by almost identical HLA-B*27 molecules in a subtype-dependent manner, allowing cytotoxic T lymphocytes to distinguish between these subtypes. For example, the human self-peptide pVIPR (RRKWRRWHL) is displayed in a single conformation by B*27:09 (not AS-associated), while B*27:05 (AS-associated) presents the peptide in a dual binding mode. In addition, differences in conformational flexibility between these subtypes might affect their stability or antigen presentation capability. We investigated B*27:04 and B*27:06, another pair of minimally distinct HLA-B*27 subtypes, to assess whether dual peptide conformations or structural dynamics could play a role in the initiation of AS. METHODS: Using X-ray crystallography, we solved the structures of pVIPR-B*27:04 and pVIPR-B*27:06 and employed isotope-edited infrared (IR) spectroscopy to probe the dynamics of these HLA-B*27 subtypes. RESULTS: As opposed to B*27:05 and B*27:09, B*27:04 (AS-associated) displays pVIPR conventionally and B*27:06 (not AS-associated) presents the peptide in a dual conformation. On the other hand, the comparison of the four HLA-B*27 subtypes using IR spectroscopy revealed that B*27:04 and B*27:05 exhibit elevated molecular dynamics when compared to the non-associated subtypes B*27:06 and B*27:09. CONCLUSION: Our results demonstrate that an increase in conformational flexibility characterizes the disease-associated subtypes B*27:04 and B*27:05. This article is protected by copyright. All rights reserved. Increased conformational flexibility characterizes HLA-B*27 subtypes associated with ankylosing spondylitis.,Loll B, Fabian H, Huser H, Hee CS, Ziegler A, Uchanska-Ziegler B, Ziegler A Arthritis Rheumatol. 2016 Jan 8. doi: 10.1002/art.39567. PMID:26748477 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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