PDBsum entry 1ydp

Immune system

PDB id: 1ydp

Contents

Protein chains

275 a.a.

100 a.a.

Ligands

ARG-ILE-ILE-PRO-ARG-HIS-LEU-GLN-LEU

Metals

_CL ×2

_CO

Waters ×427

References listed in PDB file

Key reference

Title

Crystal structure of hla-G: a nonclassical mhc class i molecule expressed at the fetal-Maternal interface.

Authors

C.S.Clements, L.Kjer-Nielsen, L.Kostenko, H.L.Hoare, M.A.Dunstone, E.Moses, K.Freed, A.G.Brooks, J.Rossjohn, J.Mccluskey.

Ref.

Proc Natl Acad Sci U S A, 2005, 102, 3360-3365. [DOI no: 10.1073/pnas.0409676102]

PubMed id

15718280

Abstract

HLA-G is a nonclassical major histocompatibility complex class I (MHC-I) molecule that is primarily expressed at the fetal-maternal interface, where it is thought to play a role in protecting the fetus from the maternal immune response. HLA-G binds a limited repertoire of peptides and interacts with the inhibitory leukocyte Ig-like receptors LIR-1 and LIR-2 and possibly with certain natural killer cell receptors. To gain further insights into HLA-G function, we determined the 1.9-A structure of a monomeric HLA-G complexed to a natural endogenous peptide ligand from histone H2A (RIIPRHLQL). An extensive network of contacts between the peptide and the antigen-binding cleft reveal a constrained mode of binding reminiscent of the nonclassical HLA-E molecule, thereby providing a structural basis for the limited peptide repertoire of HLA-G. The alpha3 domain of HLA-G, a candidate binding site for the LIR-1 and -2 inhibitory receptors, is structurally distinct from the alpha3 domains of classical MHC-I molecules, providing a rationale for the observed affinity differences for these ligands. The structural data suggest a head-to-tail mode of dimerization, mediated by an intermolecular disulfide bond, that is consistent with the observation of HLA-G dimers on the cell surface.

Figure 1.
Fig. 1. Overview of the structure of HLA-G. (A) The hc is shown in purple, [2]M in blue, and the peptide in green. The position of the Cys-42 Ser mutation is labeled. (B) Conformation of bound peptide. The corresponding 2F[o]- F[c] electron density is shown in mesh format. The peptide is in ball-and-stick format with each amino acid labeled.

Figure 4.
Fig. 4. Pocket-mediated interactions of HLA-G. HLA-G residues are shown in purple, peptide residues are shown in green, polar contacts are depicted as dashed lines, and water molecules are shown as blue spheres. (A) Pockets A and B mediating interactions with P1-Arg and P2-Ile, respectively. (B) Pockets C and D mediating interactions with P6-His and P2-Pro, respectively. (C) Pockets E and F mediating interactions with P7-Leu and P9-Leu, respectively. (D) Overview of the hydrophobic nature of the HLA-G binding cleft. Hydrophobic regions of the cleft that bind peptide are shown in green with the important anchor residue His-70 colored yellow. The pockets are labeled A-F, and the peptide is depicted as a ball-and-stick structure.