6pyv | pdb_00006pyv

Crystal Structure of HLA-B*2703-P47G in complex with LRN, a self-peptide

spinqualitylabelsall models 6pyv, resolution 1.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6pyv 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 1.45Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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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