The three-dimensional structure of HLA-B27 at 2.1 Å resolution suggests a general mechanism for tight peptide binding to MHC

Madden, Dean R.; Gorga, Joan C.; Strominger, Jack L.; Wiley, Don C.

doi:10.1016/0092-8674(92)90252-8

Cited by 639 publications

(399 citation statements)

References 65 publications

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“…Our data show that HLA-B*2705 binds three immunodominant viral epitopes in a canonical extended conformation, similar to the self peptides studied previously [10,11,21,22,29]. By doubling the number of HLA-B*2705-peptide structures (from three to six), we show how HLA-B*2705 can bind peptides in subtly different ways.…”

Section: Resultssupporting

confidence: 82%

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Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA‐B*2705

et al. 2005

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We have solved the crystal structures of three HLA‐B*2705–peptide complexes with the immunodominant viral peptides: EBV EBNA3C 258–266 (RRIYDLIEL), influenza (flu) nucleoprotein NP383–391 (SRYWAIRTR), and HIV gag 264–273 (KRWIILGLNK). Long‐term non‐progression during HIV infection has been associated with presentation by HLA‐B*2705, and T cell recognition, of the highly immunodominant KRWIILGLNK peptide. The tight hydrogen‐bonding network observed between the HLA‐B*2705 B‐pocket and the peptide P2 arginine guanadinium anchor explains why mutation of this residue during HIV infection results in loss of peptide binding, immune escape and progression to AIDS. Prominent, solvent‐exposed structures within these peptides may participate in generating T cell responses to these immunodominant epitopes. In the HLA‐B*2705 complex with flu NP383–391, the amino acid side chains of residues 4, 7 and 8 are solvent‐exposed whilst in the HIV decamer, the main‐chain bulges into the solvent around P7. Thus, HLA‐B*2705 presents viral peptides in a range of conformations. Tetrameric complexes of HLA‐B*2705 with the HIV and flu but not EBV peptides bound strongly to the killer‐Ig‐like receptor (KIR)3DL1. Substitution of EBV P8 glutamate to threonine allowed recognition by KIR3DL1. In the HLA‐B*2705–EBV structure the P8 glutamate side chain is solvent‐exposed and may inhibit KIR3DL1 binding through electrostatic forces.See accompanying Commentary: http://dx.doi.org/10.1002/eji.200425875

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Section: Resultssupporting

confidence: 82%

“…Previous crystallographic and peptide-elution studies of HLA-B*2705 derived from tissue culture have demonstrated that HLA-B*2705 almost invariably binds self peptides with an arginine at peptide position 2, this side chain being accommodated in the B-pocket [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA‐B*2705

et al. 2005

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“…Interestingly, however, analysis of the primary sequence and secondary structure predictions of the C-terminal third of hsp7Os have revealed a rather striking structural similarity to the MHC class I antigen HLA presenting molecule (Flajnik et al, 1991;Rippmann et al, 1991). MHC-class I antigen presenting protein binds peptides in an extended conformation (Madden et al, 1991(Madden et al, , 1992, as does Escherichiu coli hsp70, DnaK, with at least one peptide (Landry et al, 1992) suggesting an interaction with the peptide backbone. Binding of one hsp70, BiP, shows a preference for binding peptides rich in aliphatic, hydrophobic amino acids with a size of at least seven amino acids (Flynn et al, 1991).…”

Section: Hsp70mentioning

confidence: 99%

Heat‐shock proteins as molecular chaperones

Becker

Craig

1994

European Journal of Biochemistry

483

221

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Functional proteins within cells are normally present in their native, completely folded form. However, vital processes of protein biogenesis such as protein synthesis and translocation of proteins into intracellular compartments require the protein to exist temporarily in an unfolded or partially folded conformation. As a consequence, regions buried when a polypeptide is in its native conformation become exposed and interact with other proteins causing protein aggregation which is deleterious to the cell. To prevent aggregation as proteins become unfolded, heat‐shock proteins protect these interactive surfaces by binding to them and facilitating the folding of unfolded or nascent polypeptides. In other instances the binding of heat‐shock proteins to interactive surfaces of completely folded proteins is a crucial part of their regulation. As heat shock and other stress conditions cause cellular proteins to become partially unfolded, the ability of heat‐shock proteins to protect cells against the adverse effects of stress becomes a logical extension of their normal function as molecular chaperones.

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“…The amino acids lining the six pockets, critical for epitope binding, have previously been determined (7)(8)(9)(10). The residues at the second position and at the carboxyl terminus of the epitope, that bind within the B and F pockets, respectively, form the primary anchor residues in 86 of the 97 motifs determined by analysis of eluted peptides (͗www.syfpeithi.de/͘ and Ref.…”

Section: Motif Inferencementioning

confidence: 99%

“…This may be inferred from knowledge of the amino acid sequence of the alleles and of the residues that, from crystallographic studies, characteristically form these binding pockets (7)(8)(9)(10). We hypothesized that the motif may then be successfully inferred by comparison of these pocket-forming HLA residues in uncharacterized alleles, such as HLA-B*4201, with those equivalent HLA residues that form the same pockets in related alleles, such as HLA-B*0702, for which the peptide-binding motif has been determined.…”

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confidence: 99%

Motif Inference Reveals Optimal CTL Epitopes Presented by HLA Class I Alleles Highly Prevalent in Southern Africa

Honeyborne

Rathod

Buchli

et al. 2006

The Journal of Immunology

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HIV-specific CTL play a central role in immune control of HIV. The basis for understanding the success or failure of this immune response requires identification of the specific epitopes targeted by CTL. However, in populations most severely affected by the global epidemic, this fundamental knowledge is hindered by the lack of characterization of many of the HLA class I alleles highly prevalent in such populations. Overall, the peptide-binding motif has been determined for a small minority (9%) of HLA class I alleles, with a strong bias toward those alleles prevalent in Caucasoid populations. These studies therefore set out to define, in a South African Zulu/Xhosa population at the epicenter of the epidemic, the epitopes presented by alleles highly prevalent, but for which the peptide-binding motif had not been characterized. Using a method of motif inference, epitopes presented by four such alleles prevalent in the Zulu/Xhosa population of Durban, South Africa, namely, B*3910, B*4201, B*8101, and Cw*1801, are described. Importantly, this approach may additionally facilitate optimization of epitopes in certain instances where conflicting reports in the literature exist regarding the peptide-binding motif, such as for HLA-A*2902, also highly prevalent in southern African populations. These data indicate that the previously anomalous position of HLA-A*2902 among HLA-A alleles, outside any recognized HLA-A supertype, is artifactual, and the true position of the A*2902 motif overlaps those of the A1 and A24 supertypes.

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The three-dimensional structure of HLA-B27 at 2.1 Å resolution suggests a general mechanism for tight peptide binding to MHC

Cited by 639 publications

References 65 publications

Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA‐B*2705

Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA‐B*2705

Heat‐shock proteins as molecular chaperones

Motif Inference Reveals Optimal CTL Epitopes Presented by HLA Class I Alleles Highly Prevalent in Southern Africa

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