|
|
| (One intermediate revision not shown.) |
| Line 3: |
Line 3: |
| | <StructureSection load='1klu' size='340' side='right'caption='[[1klu]], [[Resolution|resolution]] 1.93Å' scene=''> | | <StructureSection load='1klu' size='340' side='right'caption='[[1klu]], [[Resolution|resolution]] 1.93Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1klu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KLU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KLU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1klu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KLU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KLU FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1klg|1klg]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.93Å</td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1klu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1klu OCA], [https://pdbe.org/1klu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1klu RCSB], [https://www.ebi.ac.uk/pdbsum/1klu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1klu ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1klu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1klu OCA], [https://pdbe.org/1klu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1klu RCSB], [https://www.ebi.ac.uk/pdbsum/1klu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1klu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Genetic variation in HLA-DRB1 is a cause of susceptibility to sarcoidosis type 1 (SS1) [MIM:[https://omim.org/entry/181000 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.<ref>PMID:14508706</ref>
| + | [https://www.uniprot.org/uniprot/TPIS_HUMAN TPIS_HUMAN] Defects in TPI1 are the cause of triosephosphate isomerase deficiency (TPI deficiency) [MIM:[https://omim.org/entry/190450 190450]. TPI deficiency is an autosomal recessive disorder. It is the most severe clinical disorder of glycolysis. It is associated with neonatal jaundice, chronic hemolytic anemia, progressive neuromuscular dysfunction, cardiomyopathy and increased susceptibility to infection. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ENTC3_STAAU ENTC3_STAAU]] Staphylococcal enterotoxins cause the intoxication staphylococcal food poisoning syndrome. The illness is characterized by high fever, hypotension, diarrhea, shock, and in some cases death. [[https://www.uniprot.org/uniprot/DRA_HUMAN 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. [[https://www.uniprot.org/uniprot/2B11_HUMAN 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.
| + | [https://www.uniprot.org/uniprot/TPIS_HUMAN TPIS_HUMAN] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 16: |
Line 16: |
| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kl/1klu_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kl/1klu_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| Line 33: |
Line 33: |
| | ==See Also== | | ==See Also== |
| | *[[MHC 3D structures|MHC 3D structures]] | | *[[MHC 3D structures|MHC 3D structures]] |
| | + | *[[MHC II 3D structures|MHC II 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Andersen, P S]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Mariuzza, R A]] | + | [[Category: Andersen PS]] |
| - | [[Category: Sawicki, M W]] | + | [[Category: Mariuzza RA]] |
| - | [[Category: Sette, A]] | + | [[Category: Sawicki MW]] |
| - | [[Category: Sidney, J]] | + | [[Category: Sette A]] |
| - | [[Category: Sundberg, E J]] | + | [[Category: Sidney J]] |
| - | [[Category: Cd4+ t cell]]
| + | [[Category: Sundberg EJ]] |
| - | [[Category: Enterotoxin c3]]
| + | |
| - | [[Category: Hla-dr1/tpi]]
| + | |
| - | [[Category: Human melanoma antigen]]
| + | |
| - | [[Category: Immune system-toxin complex]]
| + | |
