Limits...
Structure of human histocompatibility leukocyte antigen (HLA)-Cw4, a ligand for the KIR2D natural killer cell inhibitory receptor.

Fan QR, Wiley DC - J. Exp. Med. (1999)

Bottom Line: The structure reveals an unusual pattern of internal hydrogen bonding among peptide residues.The peptide is anchored in four specificity pockets in the cleft and secured by extensive hydrogen bonds between the peptide main chain and the cleft.The surface of HLA-Cw4 has electrostatic complementarity to the surface of the NK cell inhibitory receptor KIR2D.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA.

ABSTRACT
The crystal structure of the human class I major histocompatibility complex molecule, human histocompatibility leukocyte antigen (HLA)-Cw4, the ligand for a natural killer (NK) cell inhibitory receptor, has been determined, complexed with a nonameric consensus peptide (QYDDAVYKL). Relative to HLA-A2, the peptide binding groove is widened around the COOH terminus of the alpha 1 helix, which contains residues that determine the specificity of HLA-Cw4 for the inhibitory NK receptor, KIR2D. The structure reveals an unusual pattern of internal hydrogen bonding among peptide residues. The peptide is anchored in four specificity pockets in the cleft and secured by extensive hydrogen bonds between the peptide main chain and the cleft. The surface of HLA-Cw4 has electrostatic complementarity to the surface of the NK cell inhibitory receptor KIR2D.

Show MeSH
(a) Electropotential molecular surface (GRASP; reference 70) of the peptide binding groove of HLA-Cw4, illustrating the four specificity pockets. The surface is colored according to its potential charge: red, negatively charged and blue, positively charged, with a scale from −13 to +13 kT. (b) Molecular surface representation of HLA-Cw4, with a ball and stick model of the peptide. (c) P3 pocket as viewed from the side of the peptide groove.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2195553&req=5

Figure 5: (a) Electropotential molecular surface (GRASP; reference 70) of the peptide binding groove of HLA-Cw4, illustrating the four specificity pockets. The surface is colored according to its potential charge: red, negatively charged and blue, positively charged, with a scale from −13 to +13 kT. (b) Molecular surface representation of HLA-Cw4, with a ball and stick model of the peptide. (c) P3 pocket as viewed from the side of the peptide groove.

Mentions: The HLA-Cw4 structure differs from most known structures of class I MHC molecules in that the peptide conformation includes a pattern of internal hydrogen bonding within the peptide (Fig. 3 b). The main chain–main chain hydrogen bond between the carbonyl oxygen of P2Tyr and the NH2 group of P4Asp causes P4Asp to adopt φ and ψ angles that are found in a left-handed helix and usually observed in residues forming tight turns and kinks . All other residues of the peptide have φ and ψ angles that are typical for an extended β strand. In addition, two hydrogen bonds are also formed between a side chain carboxylate oxygen atom of P3Asp and the main chain amino groups of P4Asp and P5Ala. The side chain of P3Asp can not fit into a small D pocket 41 underneath the α2 helix and formed by the side chains of Arg97, Phe99, Arg156, and Tyr159 (Fig. 5 c). As a result, although the Cβ atom of P3Asp points toward the α2 helix, its side chain carboxylate is turned back toward the peptide, forming hydrogen bonds with the peptide main chain atoms and the side chain atoms of Arg156 (Fig. 3 b; Table ). An internal hydrogen-bonded type I turn has previously been identified in the structure of an HIV gp120 peptide bound to murine H-2Dd 4243.


Structure of human histocompatibility leukocyte antigen (HLA)-Cw4, a ligand for the KIR2D natural killer cell inhibitory receptor.

Fan QR, Wiley DC - J. Exp. Med. (1999)

(a) Electropotential molecular surface (GRASP; reference 70) of the peptide binding groove of HLA-Cw4, illustrating the four specificity pockets. The surface is colored according to its potential charge: red, negatively charged and blue, positively charged, with a scale from −13 to +13 kT. (b) Molecular surface representation of HLA-Cw4, with a ball and stick model of the peptide. (c) P3 pocket as viewed from the side of the peptide groove.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195553&req=5

Figure 5: (a) Electropotential molecular surface (GRASP; reference 70) of the peptide binding groove of HLA-Cw4, illustrating the four specificity pockets. The surface is colored according to its potential charge: red, negatively charged and blue, positively charged, with a scale from −13 to +13 kT. (b) Molecular surface representation of HLA-Cw4, with a ball and stick model of the peptide. (c) P3 pocket as viewed from the side of the peptide groove.
Mentions: The HLA-Cw4 structure differs from most known structures of class I MHC molecules in that the peptide conformation includes a pattern of internal hydrogen bonding within the peptide (Fig. 3 b). The main chain–main chain hydrogen bond between the carbonyl oxygen of P2Tyr and the NH2 group of P4Asp causes P4Asp to adopt φ and ψ angles that are found in a left-handed helix and usually observed in residues forming tight turns and kinks . All other residues of the peptide have φ and ψ angles that are typical for an extended β strand. In addition, two hydrogen bonds are also formed between a side chain carboxylate oxygen atom of P3Asp and the main chain amino groups of P4Asp and P5Ala. The side chain of P3Asp can not fit into a small D pocket 41 underneath the α2 helix and formed by the side chains of Arg97, Phe99, Arg156, and Tyr159 (Fig. 5 c). As a result, although the Cβ atom of P3Asp points toward the α2 helix, its side chain carboxylate is turned back toward the peptide, forming hydrogen bonds with the peptide main chain atoms and the side chain atoms of Arg156 (Fig. 3 b; Table ). An internal hydrogen-bonded type I turn has previously been identified in the structure of an HIV gp120 peptide bound to murine H-2Dd 4243.

Bottom Line: The structure reveals an unusual pattern of internal hydrogen bonding among peptide residues.The peptide is anchored in four specificity pockets in the cleft and secured by extensive hydrogen bonds between the peptide main chain and the cleft.The surface of HLA-Cw4 has electrostatic complementarity to the surface of the NK cell inhibitory receptor KIR2D.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA.

ABSTRACT
The crystal structure of the human class I major histocompatibility complex molecule, human histocompatibility leukocyte antigen (HLA)-Cw4, the ligand for a natural killer (NK) cell inhibitory receptor, has been determined, complexed with a nonameric consensus peptide (QYDDAVYKL). Relative to HLA-A2, the peptide binding groove is widened around the COOH terminus of the alpha 1 helix, which contains residues that determine the specificity of HLA-Cw4 for the inhibitory NK receptor, KIR2D. The structure reveals an unusual pattern of internal hydrogen bonding among peptide residues. The peptide is anchored in four specificity pockets in the cleft and secured by extensive hydrogen bonds between the peptide main chain and the cleft. The surface of HLA-Cw4 has electrostatic complementarity to the surface of the NK cell inhibitory receptor KIR2D.

Show MeSH