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From Proteopedia
Rhesus macaque MHC class I molecule Mamu-B*17-HW8
Structural highlights
DiseaseB2MG_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.[1] 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.[2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] FunctionB2MG_HUMAN Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Publication Abstract from PubMedThe MHC class I molecule Mamu-B*17 has been associated with elite control of SIV infection in rhesus macaques, akin to the protective effects described for HLA-B*57 in HIV-infected individuals. In this study, we determined the crystal structures of Mamu-B*17 in complex with eight different peptides corresponding to immunodominant SIV(mac)239-derived CD8(+) T cell epitopes: HW8 (HLEVQGYW), GW10 (GSHLEVQGYW), MW9 (MHPAQTSQW), QW9 (QTSQWDDPW), FW9 (FQWMGYELW), MF8 (MRHVLEPF), IW9 (IRYPKTFGW), and IW11 (IRYPKTFGWLW). The structures reveal that not only P2, but also P1 and P3, can be used as N-terminal anchor residues by Mamu-B*17-restricted peptides. Moreover, the N-terminal anchor residues exhibit a broad chemical specificity, encompassing basic (H and R), bulky polar aliphatic (Q), and small (T) residues. In contrast, Mamu-B*17 exhibits a very narrow preference for aromatic residues (W and F) at the C terminus, similar to that displayed by HLA-B*57. Flexibility within the whole peptide-binding groove contributes to the accommodation of these diverse peptides, which adopt distinct conformations. Furthermore, the unusually large pocket D enables compensation from other peptide residues if P3 is occupied by an amino acid with a small side chain. In addition, residues located at likely TCR contact regions present highly flexible conformations, which may impact TCR repertoire profiles. These findings provide novel insights into the structural basis of diverse peptide accommodation by Mamu-B*17 and highlight unique atomic features that might contribute to the protective effect of this MHC I molecule in SIV-infected rhesus macaques. Structural basis of diverse peptide accommodation by the rhesus macaque MHC class I molecule Mamu-B*17: insights into immune protection from simian immunodeficiency virus.,Wu Y, Gao F, Liu J, Qi J, Gostick E, Price DA, Gao GF J Immunol. 2011 Dec 15;187(12):6382-92. Epub 2011 Nov 14. PMID:22084443[15] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Macaca mulatta | Simian immunodeficiency virus | Gao F | Gao GF | Liu J | Price DA | Qi JX | Wu Y
