4gbx: Difference between revisions

Latest revision as of 02:55, 21 November 2024

Crystal structure of an immune complex at pH 6.5

Structural highlights

4gbx is a 5 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3Å
Ligands:	NAG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DMA_HUMAN Plays a critical role in catalyzing the release of class II-associated invariant chain peptide (CLIP) from newly synthesized MHC class II molecules and freeing the peptide binding site for acquisition of antigenic peptides. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO.^[1] ^[2] ^[3]

Publication Abstract from PubMed

HLA-DR molecules bind microbial peptides in an endosomal compartment and present them on the cell surface for CD4 T cell surveillance. HLA-DM plays a critical role in the endosomal peptide selection process. The structure of the HLA-DM-HLA-DR complex shows major rearrangements of the HLA-DR peptide-binding groove. Flipping of a tryptophan away from the HLA-DR1 P1 pocket enables major conformational changes that position hydrophobic HLA-DR residues into the P1 pocket. These conformational changes accelerate peptide dissociation and stabilize the empty HLA-DR peptide-binding groove. Initially, incoming peptides have access to only part of the HLA-DR groove and need to compete with HLA-DR residues for access to the P2 site and the hydrophobic P1 pocket. This energetic barrier creates a rapid and stringent selection process for the highest-affinity binders. Insertion of peptide residues into the P2 and P1 sites reverses the conformational changes, terminating selection through DM dissociation.

Crystal Structure of the HLA-DM-HLA-DR1 Complex Defines Mechanisms for Rapid Peptide Selection.,Pos W, Sethi DK, Call MJ, Schulze MS, Anders AK, Pyrdol J, Wucherpfennig KW Cell. 2012 Dec 21;151(7):1557-68. doi: 10.1016/j.cell.2012.11.025. PMID:23260142^[4]

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

References

↑ Weber DA, Evavold BD, Jensen PE. Enhanced dissociation of HLA-DR-bound peptides in the presence of HLA-DM. Science. 1996 Oct 25;274(5287):618-20. PMID:8849454
↑ Mosyak L, Zaller DM, Wiley DC. The structure of HLA-DM, the peptide exchange catalyst that loads antigen onto class II MHC molecules during antigen presentation. Immunity. 1998 Sep;9(3):377-83. PMID:9768757
↑ Nicholson MJ, Moradi B, Seth NP, Xing X, Cuny GD, Stein RL, Wucherpfennig KW. Small molecules that enhance the catalytic efficiency of HLA-DM. J Immunol. 2006 Apr 1;176(7):4208-20. PMID:16547258
↑ Pos W, Sethi DK, Call MJ, Schulze MS, Anders AK, Pyrdol J, Wucherpfennig KW. Crystal Structure of the HLA-DM-HLA-DR1 Complex Defines Mechanisms for Rapid Peptide Selection. Cell. 2012 Dec 21;151(7):1557-68. doi: 10.1016/j.cell.2012.11.025. PMID:23260142 doi:https://dx.doi.org/10.1016/j.cell.2012.11.025

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Weber DA, Evavold BD, Jensen PE. Enhanced dissociation of HLA-DR-bound peptides in the presence of HLA-DM. Science. 1996 Oct 25;274(5287):618-20. PMID:8849454

[2] Mosyak L, Zaller DM, Wiley DC. The structure of HLA-DM, the peptide exchange catalyst that loads antigen onto class II MHC molecules during antigen presentation. Immunity. 1998 Sep;9(3):377-83. PMID:9768757

[3] Nicholson MJ, Moradi B, Seth NP, Xing X, Cuny GD, Stein RL, Wucherpfennig KW. Small molecules that enhance the catalytic efficiency of HLA-DM. J Immunol. 2006 Apr 1;176(7):4208-20. PMID:16547258

[4] Pos W, Sethi DK, Call MJ, Schulze MS, Anders AK, Pyrdol J, Wucherpfennig KW. Crystal Structure of the HLA-DM-HLA-DR1 Complex Defines Mechanisms for Rapid Peptide Selection. Cell. 2012 Dec 21;151(7):1557-68. doi: 10.1016/j.cell.2012.11.025. PMID:23260142 doi:https://dx.doi.org/10.1016/j.cell.2012.11.025

[1]

[2]

[3]

[4]

@@ Line 1: / Line 1: @@
-[[Image:4gbx.jpg|left|200px]]
-{{STRUCTURE_4gbx|  PDB=4gbx  |  SCENE=  }}
+==Crystal structure of an immune complex at pH 6.5==
+<StructureSection load='4gbx' size='340' side='right'caption='[[4gbx]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4gbx]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GBX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GBX FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=4gbx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gbx OCA], [https://pdbe.org/4gbx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gbx RCSB], [https://www.ebi.ac.uk/pdbsum/4gbx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gbx ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/DMA_HUMAN DMA_HUMAN] Plays a critical role in catalyzing the release of class II-associated invariant chain peptide (CLIP) from newly synthesized MHC class II molecules and freeing the peptide binding site for acquisition of antigenic peptides. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO.<ref>PMID:8849454</ref> <ref>PMID:9768757</ref> <ref>PMID:16547258</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+HLA-DR molecules bind microbial peptides in an endosomal compartment and present them on the cell surface for CD4 T cell surveillance. HLA-DM plays a critical role in the endosomal peptide selection process. The structure of the HLA-DM-HLA-DR complex shows major rearrangements of the HLA-DR peptide-binding groove. Flipping of a tryptophan away from the HLA-DR1 P1 pocket enables major conformational changes that position hydrophobic HLA-DR residues into the P1 pocket. These conformational changes accelerate peptide dissociation and stabilize the empty HLA-DR peptide-binding groove. Initially, incoming peptides have access to only part of the HLA-DR groove and need to compete with HLA-DR residues for access to the P2 site and the hydrophobic P1 pocket. This energetic barrier creates a rapid and stringent selection process for the highest-affinity binders. Insertion of peptide residues into the P2 and P1 sites reverses the conformational changes, terminating selection through DM dissociation.
-===Crystal structure of an immune complex at pH 6.5===
+Crystal Structure of the HLA-DM-HLA-DR1 Complex Defines Mechanisms for Rapid Peptide Selection.,Pos W, Sethi DK, Call MJ, Schulze MS, Anders AK, Pyrdol J, Wucherpfennig KW Cell. 2012 Dec 21;151(7):1557-68. doi: 10.1016/j.cell.2012.11.025. PMID:23260142<ref>PMID:23260142</ref>
-{{ABSTRACT_PUBMED_23260142}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 4gbx" style="background-color:#fffaf0;"></div>
-[[4gbx]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GBX OCA].
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Pos, W.]]
+[[Category: Large Structures]]
-[[Category: Sethi, D K.]]
+[[Category: Synthetic construct]]
-[[Category: Wucherpfennig, K W.]]
+[[Category: Pos W]]
-[[Category: Antigen presentation]]
+[[Category: Sethi DK]]
-[[Category: Immune complex]]
+[[Category: Wucherpfennig KW]]
-[[Category: Immune system]]
-[[Category: Peptide editing]]
-[[Category: Peptide loading]]

4gbx: Difference between revisions

Latest revision as of 02:55, 21 November 2024

Crystal structure of an immune complex at pH 6.5

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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