6pyj

Crystal Structure of HLA-B*2705 in complex with LRN, a self-peptide

spinqualitylabelsall models 6pyj, resolution 1.44Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6pyj is a 3 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 1.44Å 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 Expression of human leukocyte antigen (HLA)-B27 is strongly associated with predisposition towards ankylosing spondylitis (AS) and other spondyloarthropathies. However, the exact involvement of HLA-B27 in disease initiation and progression remains unclear. The homodimer theory, which proposes that HLA-B27 heavy chains aberrantly form homodimers, is a central hypothesis that attempts to explain the role of HLA-B27 in disease pathogenesis. Here we examined the ability of the 8 most prevalent HLA-B27 allotypes (HLA-B*27:02 - HLA-B*27:09) to form homodimers. We observed that HLA-B*27:03, a disease-associated HLA-B27 subtype, showed a significantly reduced ability to form homodimers in comparison to all other allotypes, including the non-disease-associated/protective allotypes HLA-B*27:06 and HLA-B*27:09. We used X-ray crystallography and site-directed mutagenesis to unravel the molecular and structural mechanisms in HLA-B*27:03 that are responsible for its compromised ability to form homodimers. We show that polymorphism at position-59, which differentiates HLA-B*27:03 from all other allotypes, is responsible for its compromised ability to form homodimers. Indeed, histidine-59 in HLA-B*27:03 leads to a series of local conformational changes that act in concert to reduce the accessibility of the nearby cysteine-67, an essential amino acid residue for the formation of HLA-B27 homodimers. Considered together, the ability of both protective and disease-associated HLA-B27 allotypes to form homodimers and the failure of HLA-B*27:03 to form homodimers challenge the role of HLA-B27 homodimers in AS pathoetiology. Rather, this work implicates other features such as peptide binding and antigen presentation as pivotal mechanisms for disease pathogenesis. Allelic association with ankylosing spondylitis fails to correlate with human leukocyte antigen B27 homodimer formation.,Lim Kam Sian TCC, Indumathy S, Halim H, Greule A, Cryle MJ, Bowness P, Rossjohn J, Gras S, Purcell AW, Schittenhelm RB J Biol Chem. 2019 Nov 18. pii: RA119.010257. doi: 10.1074/jbc.RA119.010257. PMID:31740583 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-2 microglobulin 3D structures MHC 3D structures MHC I 3D structures

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