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• W1978766025 abstract "We describe structural studies of the human leukocyte antigen DR52a, HLA-DRA/DRB3*0101, in complex with an N-terminal human platelet integrin αIIBβIII glycoprotein peptide which contains a Leu/Pro dimorphism. The 33:Leu dimorphism is the epitope for the T cell directed response in neonatal alloimmune thrombocytopenia and post-transfusion purpura in individuals with the αIIBβIII 33:Pro allele, and defines the unidirectional alloimmune response. This condition is always associated with DR52a. The crystallographic structure has been refined to 2.25 Å. There are two αβ heterodimers to the asymmetric unit in space group P41212. The molecule is characterized by two prominent hydrophobic pockets at either end of the peptide binding cleft and a deep, narrower and highly charged P4 opening underneath the beta 1 chain. Further, the peptide in the second molecule displays a sharp upward turn after pocket P9. The structure reveals the role of pockets and the distinctive basic P4 pocket, shared by DR52a and DR3, in selecting their respective binding peptide repertoire. We observe an interesting switch in a residue from the canonically assigned pocket 6 seen in prior class II structures to pocket 4. This occludes the P6 pocket helping to explain the distinctive “1–4–9” peptide binding motif. A β57 Asp → Val substitution abrogates the salt-bridge to α76 Arg and along with a hydrophobic β37 is important in shaping the P9 pocket. DRB3*0101 and DRB1*0301 belong to an ancestral haplotype and are associated with many autoimmune diseases linked to antigen presentation, but whereas DR3 is susceptible to type 1 diabetes DR52a is not. This dichotomy is explored for clues to the disease." @default.
• W1978766025 created "2016-06-24" @default.
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• W1978766025 creator A5054495834 @default.
• W1978766025 creator A5069785361 @default.
• W1978766025 date "2007-08-01" @default.
• W1978766025 modified "2023-10-01" @default.
• W1978766025 title "Crystallographic Structure of the Human Leukocyte Antigen DRA, DRB3*0101: Models of a Directional Alloimmune Response and Autoimmunity" @default.
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• W1978766025 doi "https://doi.org/10.1016/j.jmb.2007.05.025" @default.
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