1rk0
From Proteopedia
Mhc Class I H-2Kb Heavy Chain Complexed With beta-2 Microglobulin and Herpes Simplex Virus Glycoprotein B peptide
Structural highlights
Function[HA1B_MOUSE] Involved in the presentation of foreign antigens to the immune system. [GB_HHV1F] Envelope glycoprotein that forms spikes at the surface of virion envelope. Essential for the initial attachment to heparan sulfate moities of the host cell surface proteoglycans. Involved in fusion of viral and cellular membranes leading to virus entry into the host cell. Following initial binding of gD to one of its receptors, membrane fusion is mediated by the fusion machinery composed at least of gB and the heterodimer gH/gL. May also be involved in the fusion between the virion envelope and the outer nuclear membrane during virion egress. Also plays a role, together with gK, in virus-induced cell-to-cell fusion (syncytia formation) (By similarity).[1] [B2MG_MOUSE] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. 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 PubMedMajor histocompatibility complex (MHC) class I variants H-2K(b) and H-2K(bm8) differ primarily in the B pocket of the peptide-binding groove, which serves to sequester the P2 secondary anchor residue. This polymorphism determines resistance to lethal herpes simplex virus (HSV-1) infection by modulating T cell responses to the immunodominant glycoprotein B(498-505) epitope, HSV8. We studied the molecular basis of these effects and confirmed that T cell receptors raised against K(b)-HSV8 cannot recognize H-2K(bm8)-HSV8. However, substitution of Ser(P2) to Glu(P2) (peptide H2E) reversed T cell receptor (TCR) recognition; H-2K(bm8)-H2E was recognized whereas H-2K(b)-H2E was not. Insight into the structural basis of this discrimination was obtained by determining the crystal structures of all four MHC class I molecules in complex with bound peptide (pMHCs). Surprisingly, we find no concerted pMHC surface differences that can explain the differential TCR recognition. However, a correlation is apparent between the recognition data and the underlying peptide-binding groove chemistry of the B pocket, revealing that secondary anchor residues can profoundly affect TCR engagement through mechanisms distinct from the alteration of the resting state conformation of the pMHC surface. Structural basis for the restoration of TCR recognition of an MHC allelic variant by peptide secondary anchor substitution.,Miley MJ, Messaoudi I, Metzner BM, Wu Y, Nikolich-Zugich J, Fremont DH J Exp Med. 2004 Dec 6;200(11):1445-54. Epub 2004 Nov 22. PMID:15557346[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Large Structures | Lk3 transgenic mice | Fremont, D H | Messaoudi, I | Miley, M J | Nikolich-Zugich, J | Class i | Herpes | Immune system | Mhc | Tcr | Virus
