3VH8

KIR3DL1 in complex with HLA-B*5701

Summary for 3VH8

• Entry DOI: 10.2210/pdb3vh8/pdb
• Descriptor: HLA class I histocompatibility antigen, B-57 alpha chain, Beta-2-microglobulin, peptide of Ig kappa chain C region, ... (6 entities in total)
• Functional Keywords: immunoglobulin fold, natural killer cell receptor, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 159888.44

Authors

Vivian, J.P.,Rossjohn, J. (deposition date: 2011-08-24, release date: 2011-10-26, Last modification date: 2024-11-20)

Primary citation

Vivian, J.P.,Duncan, R.C.,Berry, R.,O'Connor, G.M.,Reid, H.H.,Beddoe, T.,Gras, S.,Saunders, P.M.,Olshina, M.A.,Widjaja, J.M.L.,Harpur, C.M.,Lin, J.,Maloveste, S.M.,Price, D.A.,Lafont, B.A.P.,McVicar, D.W.,Clements, C.S.,Brooks, A.G.,Rossjohn, J.
Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B
Nature, 479:401-405, 2011

PubMed Abstract: Members of the killer cell immunoglobulin-like receptor (KIR) family, a large group of polymorphic receptors expressed on natural killer (NK) cells, recognize particular peptide-laden human leukocyte antigen (pHLA) class I molecules and have a pivotal role in innate immune responses. Allelic variation and extensive polymorphism within the three-domain KIR family (KIR3D, domains D0-D1-D2) affects pHLA binding specificity and is linked to the control of viral replication and the treatment outcome of certain haematological malignancies. Here we describe the structure of a human KIR3DL1 receptor bound to HLA-B*5701 complexed with a self-peptide. KIR3DL1 clamped around the carboxy-terminal end of the HLA-B*5701 antigen-binding cleft, resulting in two discontinuous footprints on the pHLA. First, the D0 domain, a distinguishing feature of the KIR3D family, extended towards β2-microglobulin and abutted a region of the HLA molecule with limited polymorphism, thereby acting as an 'innate HLA sensor' domain. Second, whereas the D2-HLA-B*5701 interface exhibited a high degree of complementarity, the D1-pHLA-B*5701 contacts were suboptimal and accommodated a degree of sequence variation both within the peptide and the polymorphic region of the HLA molecule. Although the two-domain KIR (KIR2D) and KIR3DL1 docked similarly onto HLA-C and HLA-B respectively, the corresponding D1-mediated interactions differed markedly, thereby providing insight into the specificity of KIR3DL1 for discrete HLA-A and HLA-B allotypes. Collectively, in association with extensive mutagenesis studies at the KIR3DL1-pHLA-B*5701 interface, we provide a framework for understanding the intricate interplay between peptide variability, KIR3D and HLA polymorphism in determining the specificity requirements of this essential innate interaction that is conserved across primate species.

PubMed: 22020283
DOI: 10.1038/nature10517

Experimental method

X-RAY DIFFRACTION (1.8 Å)