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==Human class II MHC protein HLA-DR1 bound to a designed peptide related to influenza virus hemagglutinin, FVKQNA(MAA)AL, in complex with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)==
==Human class II MHC protein HLA-DR1 bound to a designed peptide related to influenza virus hemagglutinin, FVKQNA(MAA)AL, in complex with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)==
<StructureSection load='1pyw' size='340' side='right' caption='[[1pyw]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
<StructureSection load='1pyw' size='340' side='right'caption='[[1pyw]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1pyw]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Staam Staam]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PYW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1PYW FirstGlance]. <br>
<table><tr><td colspan='2'>[[1pyw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Aichi/2/1968(H3N2)) Influenza A virus (A/Aichi/2/1968(H3N2))] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_Mu50 Staphylococcus aureus subsp. aureus Mu50]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PYW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PYW FirstGlance]. <br>
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MAA:N-METHYL-L-ALANINE'>MAA</scene></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]] 2.1&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dlh|1dlh]], [[1klu|1klu]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MAA:N-METHYL-L-ALANINE'>MAA</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HLA-DRA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HLA-DRB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ENTC3 OR SAV2009 OR SA1817 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158878 STAAM])</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=1pyw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pyw OCA], [https://pdbe.org/1pyw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pyw RCSB], [https://www.ebi.ac.uk/pdbsum/1pyw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pyw ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pyw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pyw OCA], [http://pdbe.org/1pyw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1pyw RCSB], [http://www.ebi.ac.uk/pdbsum/1pyw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1pyw ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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/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.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/py/1pyw_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/py/1pyw_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>
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==See Also==
==See Also==
*[[Major histocompatibility complex|Major histocompatibility complex]]
*[[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: Staam]]
[[Category: Large Structures]]
[[Category: Chan, I C]]
[[Category: Staphylococcus aureus subsp. aureus Mu50]]
[[Category: DeOliveira, D B]]
[[Category: Chan IC]]
[[Category: Mariuzza, R A]]
[[Category: DeOliveira DB]]
[[Category: Stern, L J]]
[[Category: Mariuzza RA]]
[[Category: Stone, J D]]
[[Category: Stern LJ]]
[[Category: Sundberg, E J]]
[[Category: Stone JD]]
[[Category: Svendsen, J]]
[[Category: Sundberg EJ]]
[[Category: Zavala-Ruiz, Z]]
[[Category: Svendsen J]]
[[Category: Antigen]]
[[Category: Zavala-Ruiz Z]]
[[Category: Hemagglutinin]]
[[Category: Hla-dr1]]
[[Category: Immune system-protein binding-toxin complex]]
[[Category: Influenza]]
[[Category: Major histocompatibility protein complex]]
[[Category: Mhc class ii]]
[[Category: Superantigen]]

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