1pyw

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[[Image:1pyw.gif|left|200px]]
[[Image:1pyw.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1pyw |SIZE=350|CAPTION= <scene name='initialview01'>1pyw</scene>, resolution 2.1&Aring;
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The line below this paragraph, containing "STRUCTURE_1pyw", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MAA:N-METHYLALANINE'>MAA</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY=
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or leave the SCENE parameter empty for the default display.
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|GENE= HLA-DRA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), HLA-DRB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), ENTC3 OR SAV2009 OR SA1817 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 Staphylococcus aureus])
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-->
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|DOMAIN=
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{{STRUCTURE_1pyw| PDB=1pyw | SCENE= }}
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|RELATEDENTRY=[[1dlh|1DLH]], [[1klu|1KLU]]
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|RESOURCES=<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://www.ebi.ac.uk/pdbsum/1pyw PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pyw RCSB]</span>
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}}
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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)'''
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[[Category: Svendsen, J.]]
[[Category: Svendsen, J.]]
[[Category: Zavala-Ruiz, Z.]]
[[Category: Zavala-Ruiz, Z.]]
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[[Category: antigen]]
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[[Category: Antigen]]
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[[Category: hemagglutinin]]
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[[Category: Hemagglutinin]]
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[[Category: hla-dr1]]
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[[Category: Hla-dr1]]
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[[Category: influenza]]
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[[Category: Influenza]]
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[[Category: major histocompatibility protein complex]]
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[[Category: Major histocompatibility protein complex]]
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[[Category: mhc class ii]]
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[[Category: Mhc class ii]]
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[[Category: peptide]]
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[[Category: Peptide]]
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[[Category: superantigen]]
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[[Category: Superantigen]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:39:39 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:06:30 2008''
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Revision as of 02:39, 3 May 2008

Template:STRUCTURE 1pyw

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)


Overview

Crystal structures of the class II major histocompatibilty complex (MHC) protein, HLA-DR1, generally show a tight fit between MHC and bound peptide except in the P6/P7 region of the peptide-binding site. In this region, there is a shallow water-filled pocket underneath the peptide and between the pockets that accommodate the P6 and P7 side chains. We investigated the properties of this pocket with the idea of engineering substitutions into the corresponding region of peptide antigens to increase their binding affinity for HLA-DR1. We investigated d-amino acids and N-alkyl modifications at both the P6 and P7 positions of the peptide and found that binding of peptides to HLA-DR1 could be increased by incorporating an N-methyl substitution at position 7 of the peptide. The crystal structure of HLA-DR1 bound to a peptide containing a P7 N-methyl alanine was determined. The N-methyl group orients in the P6/P7 pocket, displacing one of the waters usually bound in this pocket. The structure shows that the substitution does not alter the conformation of the bound peptide, which adopts the usual polyproline type II helix. An antigenic peptide carrying the N-methyl modification is taken up by antigen-presenting cells and loaded onto endogenous class II MHC molecules for presentation, and the resultant MHC-peptide complexes activate antigen-specific T-cells. These results suggest a possible strategy for increasing the affinity of weakly immunogenic peptides that might be applicable to the development of vaccines and diagnostic reagents.

About this Structure

1PYW is a Protein complex structure of sequences from Homo sapiens and Staphylococcus aureus. Full crystallographic information is available from OCA.

Reference

Exploration of the P6/P7 region of the peptide-binding site of the human class II major histocompatability complex protein HLA-DR1., Zavala-Ruiz Z, Sundberg EJ, Stone JD, DeOliveira DB, Chan IC, Svendsen J, Mariuzza RA, Stern LJ, J Biol Chem. 2003 Nov 7;278(45):44904-12. Epub 2003 Sep 1. PMID:12952957 Page seeded by OCA on Sat May 3 05:39:39 2008

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