Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 Å resolution

Saper, Mark A.; Björkman, Pamela J.; Wiley, Don C.

doi:10.1016/0022-2836(91)90567-p

Cited by 1,031 publications

(823 citation statements)

References 73 publications

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“…Three strong hydrophobic clusters are associated with this concavity, 2 of which are at the interface of the a, a2 and P2m domains. Table 8B lists a1 a2 residues of these 2 and compares them to residues observed at the interface with P2m (Saper et al, 1991). As in the previous case, there is agreement between residues observed at the &m interface and those calculated on the basis of hydrophobicity.…”

Section: Applicationssupporting

confidence: 68%

“…Both of these molecules are of considerable therapeutic interest as potential targets for immunological modulation. The analysis of HLA considered the a , and a2 domains (residues 1-182), which are the 2 parallel a-helices atop a @-sheet forming a cleft as the expected antigen-binding site (Saper et al, 1991). The analysis of CD4 considered the N-terminal fragment comprising 2 domains (Vl, V2) of the 4 calculated immunoglobulin-like extracellular domains (Ryu et al, 1990;Wang et al, 1990).…”

Section: Applicationsmentioning

confidence: 99%

“…Comparison of HLA a (1)a (2) residues containing atoms observed at the interface with p(2) microglobulin (Saper et al, 1991) to those of the calculated strongest hydrophobic cluster outside the cleft. Boldface type indicates agreement between predicted and observed residues.…”

Section: Applicationsmentioning

confidence: 99%

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A role for surface hydrophobicity in protein‐protein recognition

1994

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The role of hydrophobicity as a determinant of protein-protein interactions is examined. Surfaces of apo-protein targets comprising 9 classes of enzymes, 7 antibody fragments, hirudin, growth hormone, and retinol-binding protein, and their associated ligands with available X-ray structures for their complexed forms, are scanned to determine clusters of surface-accessible amino acids. Clusters of surface residues are ranked on the basis of the hydrophobicity of their constituent amino acids. The results indicate that the location of the co-crystallized ligand is commonly found to correspond with one of the strongest hydrophobic clusters on the surface of the target molecule. In 25 of 38 cases, the correspondence is exact, with the position of the most hydrophobic cluster coinciding with more than one-third of the surface buried by the bound ligand. The remaining 13 cases demonstrate this correspondence within the top 6 hydrophobic clusters. These results suggest that surface hydrophobicity can be used to identify regions of a protein's surface most likely to interact with a binding ligand. This fast and simple procedure may be useful for identifying small sets of well-defined loci for possible ligand attachment.

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Section: Applicationssupporting

confidence: 68%

Section: Applicationsmentioning

confidence: 99%

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A role for surface hydrophobicity in protein‐protein recognition

1994

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“…The peptide-binding domain is supported by the membrane proximal Ig-like domains, and is positioned distal from the membrane surface for interaction with its ligand, the T cell receptor. For most class I and class I1 MHC molecules, specific positions (or anchors) in the bound peptide are conserved (Rammensee et al, 1995), often corresponding to specific pockets in the peptide binding groove of the MHC molecule that accommodate peptide side chains of a certain size and charge (Saper et al, 1991;Matsumura et al, 1992a). In general, class I1 MHC molecules will bind peptides that have certain residues located within a nine residue ''core" motif.…”

mentioning

confidence: 99%

Engineering protein for X‐ray crystallography: The murine major histocompatibility complex class II molecule I‐A^d

et al. 1998

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Class I1 Major Histocompatibility (MHC) molecules are cell surface heterodimeric glycoproteins that play a central role in the immune response by presenting peptide antigens for surveillance by T cells. Due to the inherent instability of the class I1 MHC heterodimer, and its dependence on bound peptide for proper assembly, the production of electrophoretically pure samples of class I1 MHC proteins in complex with specific peptides has been problematic. A soluble form of the murine class I1 MHC molecule, I-Ad, with a leucine zipper tail added to each chain to enhance dimer assembly and secretion, has been produced in Drosophila melanogaster SC2 cells. To facilitate peptide loading, a high affinity ovalbumin peptide was covalently engineered to be attached by a six-residue linker to the amino terminus of the I-AdP chain. This modified I-Ad molecule was purified using preparative E F and one fraction, after removal of the leucine zipper tails, produced crystals suitable for X-ray crystallographic analysis. The protein engineering and purification methods described here should be of general value for the expression of I-A and other class I1 MHC-peptide complexes.

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“…It is now well established that the association with peptide fragments, either endogenously processed or exogenously added, enhances the structural stability of the MHC class I proteins [2][3][4][5]. X-Ray crystallographic analysis of the three-dimensional structures of human MHC proteins, HLA-A2 [6,7]. HLA-Aw68 [8] and HLA-B27 [9] have revealed the presence of additional electron density corresponding to one or more peptides in the binding groove formed by the cz t, ~z, helices and the eight-stranded ,8-sheet of the MHC heavy chain.…”

Section: Introductionmentioning

confidence: 99%

Do antigenic peptides have a unique sense of direction inside the MHC binding groove? A molecular modelling study

Bulusu

Roques

1992

FEBS Letters

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In the models suggested recently for antigenic peptides binding in the ~, ~, groove of MHC class I molecules, the orientation of the peptide has been shown uniquely as: the N~C vector of the peptide being parallel to the N~C vector of the ~t~ helix of MHC, Here, v~e demonstrate ~hat the reverse orientation of the peptide is equally probable. This hypothesis is supported by molecular modelling calculations and computer graphic analyses on a routine class I MHC molecule H-SK ° and its complexes with a restricted peptide RYLENGKETLQ. Analysis of the complementary interactions between the peptid¢ residues and the amino acid side chains lining the MHC groove shows that the binding orientation of the peptide may be allele-specific and could depend on the sequence and structure of" the antigenic epitope.

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Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 Å resolution

Cited by 1,031 publications

References 73 publications

A role for surface hydrophobicity in protein‐protein recognition

A role for surface hydrophobicity in protein‐protein recognition

Engineering protein for X‐ray crystallography: The murine major histocompatibility complex class II molecule I‐A^d

Do antigenic peptides have a unique sense of direction inside the MHC binding groove? A molecular modelling study

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Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 Å resolution

Cited by 1,031 publications

References 73 publications

A role for surface hydrophobicity in protein‐protein recognition

A role for surface hydrophobicity in protein‐protein recognition

Engineering protein for X‐ray crystallography: The murine major histocompatibility complex class II molecule I‐Ad

Do antigenic peptides have a unique sense of direction inside the MHC binding groove? A molecular modelling study

Contact Info

Product

Resources

About

Engineering protein for X‐ray crystallography: The murine major histocompatibility complex class II molecule I‐A^d