2xn9

From Proteopedia

Jump to: navigation, search
2xn9, resolution 2.30Å ()
Ligands: ,
Related: 1d6e, 1enf, 2esv, 1seb, 1jws, 1h15, 1f77, 2seb, 2ak4, 2gj6, 2wbj, 1klu, 1fyt, 1pyw, 1j8h, 1klg, 2g9h, 1ktk, 1dlh, 2bnq, 1d5z, 2eyr, 1t5x, 1a6a, 1kg0, 1bx2, 1d5m, 1lo5, 1hxy, 1hqr, 1qrn, 2bnr, 1kgc, 2cdg, 1fv1, 1sjh, 2eys, 2bnu, 1jwm, 2cdf, 1mi5, 1ymm, 1r5i, 1zgl, 1ewc, 1t5w, 1d5x, 2axh, 1aqd, 2eyt, 1sje, 1oga, 1jwu, 2cde, 2xna


Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

CRYSTAL STRUCTURE OF THE TERNARY COMPLEX BETWEEN HUMAN T CELL RECEPTOR, STAPHYLOCOCCAL ENTEROTOXIN H AND HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II

Publication Abstract from PubMed

Superantigens (SAgs) are bacterial toxins that interact with immunoreceptors, T cell receptor (TCR) and major histocompatibility complex (MHC) class II, conventionally through the variable beta-domain of TCR (TCRVbeta). They induce a massive release of cytokines, which can lead to diseases such as food poisoning and toxic shock syndrome. In this study, we report the X-ray structure of the ternary complex between staphylococcal enterotoxin H (SEH) and its human receptors, MHC class II and TCR. The structure demonstrates that SEH predominantly interacts with the variable alpha-domain of TCR (TCRValpha), which is supported by nuclear magnetic resonance (NMR) analyses. Furthermore, there is no contact between MHC and TCR upon complex formation. Structural analyses suggest that the major contact points to TCRValpha are conserved among other bacterial SAgs. Consequently, a new dimension of SAg biology emerges, suggesting that in addition to the conventional interactions with the TCRVbeta domain, SAgs can also activate T cells through the TCRValpha domain.

The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation., Saline M, Rodstrom KE, Fischer G, Orekhov VY, Karlsson BG, Lindkvist-Petersson K, Nat Commun. 2010 Nov 16;1:119. PMID:21081917

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Disease

[2B11_HUMAN] Genetic variation in HLA-DRB1 is a cause of susceptibility to sarcoidosis type 1 (SS1) [MIM:181000]. Sarcoidosis is an idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved.[1]

Function

[ETXH_STAAU] Staphylococcal enterotoxins cause the intoxication staphylococcal food poisoning syndrome. The illness characterized by high fever, hypotension, diarrhea, shock, and in some cases death. [DRA_HUMAN] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading. [2B11_HUMAN] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route; where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules; and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments; exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides; autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs; other cells of the gastrointestinal tract; such as epithelial cells; express MHC class II molecules and CD74 and act as APCs; which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen; three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs; CD74 undergoes a sequential degradation by various proteases; including CTSS and CTSL; leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells; the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules; increased acidification produces increased proteolysis and efficient peptide loading.

About this Structure

2xn9 is a 6 chain structure with sequence from Homo sapiens and Staphylococcus aureus. Full crystallographic information is available from OCA.

See Also

Reference

  • Saline M, Rodstrom KE, Fischer G, Orekhov VY, Karlsson BG, Lindkvist-Petersson K. The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation. Nat Commun. 2010 Nov 16;1:119. PMID:21081917 doi:10.1038/ncomms1117
  1. Rossman MD, Thompson B, Frederick M, Maliarik M, Iannuzzi MC, Rybicki BA, Pandey JP, Newman LS, Magira E, Beznik-Cizman B, Monos D. HLA-DRB1*1101: a significant risk factor for sarcoidosis in blacks and whites. Am J Hum Genet. 2003 Oct;73(4):720-35. Epub 2003 Aug 20. PMID:14508706 doi:10.1086/378097

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools