5ib5

Crystal structure of HLA-B*27:09 complexed with the self-peptide pVIPR and Copper

spinqualitylabelsall models 5ib5, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ib5 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.49Å Ligands: CL, CU, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 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 Conformational changes of major histocompatibility complex (MHC) antigens have the potential to be recognized by T cells and may arise from polymorphic variation of the MHC molecule, the binding of modifying ligands, or both. Here, we investigated whether metal ions could affect allele-dependent structural variation of the two minimally distinct human leukocyte antigen (HLA)-B*27:05 and HLA-B*27:09 subtypes, which exhibit differential association with the rheumatic disease ankylosing spondylitis (AS). We employed NMR spectroscopy and X-ray crystallography coupled with ensemble refinement to study the AS-associated HLA-B*27:05 subtype and the AS non-associated HLA-B* 27:09 in complex with the self-peptide pVIPR (RRKWRRWHL). Both techniques revealed that pVIPR exhibits a higher degree of flexibility when complexed with HLA-B* 27:05 than with HLA-B*27:09. Furthermore, we found that the binding of the metal ions Cu2+ or Ni2+, but not Mn2+, Zn2+, or Hg2+ affects the structure of a pVIPR-bound HLA-B*27 molecule in a subtype-dependent manner. In HLA-B*27:05, the metals triggered conformational reorientations of pVIPR, but no such structural changes were observed in the HLA-B*27:09 subtype, with or without bound metal ion. These observations provide the first demonstration that not only MHC class II, but also class I molecules can undergo metal ion-induced conformational alterations. Our findings suggest that metals may have role in triggering rheumatic diseases such as AS and also have implications for the molecular basis of metal-induced hypersensitivities and allergies. Metal-triggered conformational reorientation of a self-peptide bound to a disease-associated HLA-B*27 subtype.,Driller R, Ballaschk M, Schmieder P, Uchanska-Ziegler B, Ziegler A, Loll B J Biol Chem. 2019 Jul 11. pii: RA119.008937. doi: 10.1074/jbc.RA119.008937. PMID:31296658 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-2 microglobulin 3D structures

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