3cdg
From Proteopedia
Human CD94/NKG2A in complex with HLA-E
Structural highlights
Disease[B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:241600]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.[1] Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.[2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Function[NKG2A_HUMAN] Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. [HLAE_HUMAN] Preferably binds to a peptide derived from the signal sequence of most HLA-A, -B, -C and -G molecules. [KLRD1_HUMAN] Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. [B2MG_HUMAN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. [HLAG_HUMAN] Involved in the presentation of foreign antigens to the immune system. Plays a role in maternal tolerance of the fetus by mediating protection from the deleterious effects of natural killer cells, cytotoxic T-lymphocytes, macrophages and mononuclear cells. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe recognition of human leukocyte antigen (HLA)-E by the heterodimeric CD94-NKG2 natural killer (NK) receptor family is a central innate mechanism by which NK cells monitor the expression of other HLA molecules, yet the structural basis of this highly specific interaction is unclear. Here, we describe the crystal structure of CD94-NKG2A in complex with HLA-E bound to a peptide derived from the leader sequence of HLA-G. The CD94 subunit dominated the interaction with HLA-E, whereas the NKG2A subunit was more peripheral to the interface. Moreover, the invariant CD94 subunit dominated the peptide-mediated contacts, albeit with poor surface and chemical complementarity. This unusual binding mode was consistent with mutagenesis data at the CD94-NKG2A-HLA-E interface. There were few conformational changes in either CD94-NKG2A or HLA-E upon ligation, and such a "lock and key" interaction is typical of innate receptor-ligand interactions. Nevertheless, the structure also provided insight into how this interaction can be modulated by subtle changes in the peptide ligand or by the pairing of CD94 with other members of the NKG2 family. Differences in the docking strategies used by the NKG2D and CD94-NKG2A receptors provided a basis for understanding the promiscuous nature of ligand recognition by NKG2D compared with the fidelity of the CD94-NKG2 receptors. CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence.,Petrie EJ, Clements CS, Lin J, Sullivan LC, Johnson D, Huyton T, Heroux A, Hoare HL, Beddoe T, Reid HH, Wilce MC, Brooks AG, Rossjohn J J Exp Med. 2008 Mar 17;205(3):725-35. Epub 2008 Mar 10. PMID:18332182[15] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Large Structures | Beddoe, T | Brooks, A G | Clements, C S | Heroux, A | Hoare, H L | Huyton, T | Johnson, D | Lin, J | Petrie, E J | Reid, H H | Rossjohn, J | Sullivan, L C | Wilce, M C.J | Alternative splicing | C-type lectin | Disease mutation | Glycation | Glycoprotein | Immune response | Immune system | Immunity | Immunoglobulin domain | Membrane | Mhc | Mhc i | Nk cell receptor | Polymorphism | Pyrrolidone carboxylic acid | Secreted | Signal-anchor | Transmembrane
