1q94
From Proteopedia
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Structures of HLA-A*1101 in complex with immunodominant nonamer and decamer HIV-1 epitopes clearly reveal the presence of a middle anchor residue
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Overview
HLA-A*1101 is one of the most common human class I alleles worldwide. An, increased frequency of HLA-A*1101 has been observed in cohorts of female, sex workers from Northern Thailand who are highly exposed to HIV-1 and yet, have remained persistently seronegative. In view of this apparent, association of HLA-A*1101 with resistance to acquisition of HIV-1, infection, and given the importance of eliciting strong CTL responses to, control and eliminate HIV-1, we have determined the crystal structure of, HLA-A*1101 complexed with two immunodominant HIV-1 CTL epitopes: the, nonamer reverse transcriptase(313-321) (AIFQSSMTK) and decamer Nef(73-82), (QVPLRPMTYK) peptides. The structures confirm the presence of primary, anchor residues P2-Ile/-Val and P9-/P10-Lys, and also clearly reveal the, presence of secondary anchor residues P6-Ser for reverse transcriptase and, P7-Met for Nef. The overall backbone conformation of both peptides is, defined as two bulges that are separated by a more buried middle residue., In this study, we discuss how this topology may offer functional, advantages in the selection and presentation of HIV-1 CTL epitopes by, HLA-A*1101. Overall, this structural analysis permits a more accurate, definition of the peptide-binding motif of HLA-A*1101, the, characterization of its antigenic surface, and the correlation of, molecular determinants with resistance to HIV-1 infection. These studies, are relevant for the rational design of HLA-A*1101-restricted CTL epitopes, with improved binding and immunological properties for the development of, HIV-1 vaccines.
Disease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142800], Ankylosing spondylitis, susceptibility to, 1 OMIM:[142800], Hypoproteinemia, hypercatabolic OMIM:[109700], Stevens-Johnson syndrome, susceptibility to OMIM:[142800]
About this Structure
1Q94 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structures of HLA-A*1101 complexed with immunodominant nonamer and decamer HIV-1 epitopes clearly reveal the presence of a middle, secondary anchor residue., Li L, Bouvier M, J Immunol. 2004 May 15;172(10):6175-84. PMID:15128805
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