1kcg
From Proteopedia
NKG2D in complex with ULBP3
Structural highlights
Function[NKG2D_HUMAN] Receptor for MICA, MICB, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4. Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. Involved in the immune surveillance exerted by T- and B-lymphocytes. [N2DL3_HUMAN] Ligand for the NKG2D receptor, together with at least ULBP1 and ULBP2. ULBPs activate multiple signaling pathways in primary NK cells, resulting in the production of cytokines and chemokines. Binding of ULBPs ligands to NKG2D induces calcium mobilization and activation of the JAK2, STAT5, ERK and PI3K kinase/Akt signal transduction pathway. Has lower affinity for NKG2D compared to ULBP1 and ULBP2 and induces weaker signaling responses than does ULBP2 or ULBP1. 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 PubMedNKG2D is known to trigger the natural killer (NK) cell lysis of various tumor and virally infected cells. In the NKG2D/ULBP3 complex, the structure of ULBP3 resembles the alpha1 and alpha2 domains of classical MHC molecules without a bound peptide. The lack of alpha3 and beta2m domains is compensated by replacing two hydrophobic patches at the underside of the class I MHC-like beta sheet floor with a group of hydrophilic and charged residues in ULBP3. NKG2D binds diagonally across the ULBP3 alpha helices, creating a complementary interface, an asymmetrical subunit orientation, and local conformational adjustments in the receptor. The interface is stabilized primarily by hydrogen bonds and hydrophobic interactions. Unlike the KIR receptors that recognize a conserved HLA region by a lock-and-key mechanism, NKG2D recognizes diverse ligands by an induced-fit mechanism. Conformational plasticity revealed by the cocrystal structure of NKG2D and its class I MHC-like ligand ULBP3.,Radaev S, Rostro B, Brooks AG, Colonna M, Sun PD Immunity. 2001 Dec;15(6):1039-49. PMID:11754823[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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