6gh4: Difference between revisions
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==HLA-E*01:03 in complex with the Mtb44 peptide variant: Mtb44*P2-Gln.== | |||
<StructureSection load='6gh4' size='340' side='right'caption='[[6gh4]], [[Resolution|resolution]] 2.16Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6gh4]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mycobacteriaceae Mycobacteriaceae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GH4 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]] 2.16Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6gh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gh4 OCA], [https://pdbe.org/6gh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gh4 RCSB], [https://www.ebi.ac.uk/pdbsum/6gh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gh4 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HLAE_HUMAN HLAE_HUMAN] Preferably binds to a peptide derived from the signal sequence of most HLA-A, -B, -C and -G molecules. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Through major histocompatibility complex class Ia leader sequence-derived (VL9) peptide binding and CD94/NKG2 receptor engagement, human leucocyte antigen E (HLA-E) reports cellular health to NK cells. Previous studies demonstrated a strong bias for VL9 binding by HLA-E, a preference subsequently supported by structural analyses. However, Mycobacteria tuberculosis (Mtb) infection and Rhesus cytomegalovirus-vectored SIV vaccinations revealed contexts where HLA-E and the rhesus homologue, Mamu-E, presented diverse pathogen-derived peptides to CD8(+) T cells, respectively. Here we present crystal structures of HLA-E in complex with HIV and Mtb-derived peptides. We show that despite the presence of preferred primary anchor residues, HLA-E-bound peptides can adopt alternative conformations within the peptide binding groove. Furthermore, combined structural and mutagenesis analyses illustrate a greater tolerance for hydrophobic and polar residues in the primary pockets than previously appreciated. Finally, biochemical studies reveal HLA-E peptide binding and exchange characteristics with potential relevance to its alternative antigen presenting function in vivo. | |||
Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding.,Walters LC, Harlos K, Brackenridge S, Rozbesky D, Barrett JR, Jain V, Walter TS, O'Callaghan CA, Borrow P, Toebes M, Hansen SG, Sacha J, Abdulhaqq S, Greene JM, Fruh K, Marshall E, Picker LJ, Jones EY, McMichael AJ, Gillespie GM Nat Commun. 2018 Aug 7;9(1):3137. doi: 10.1038/s41467-018-05459-z. PMID:30087334<ref>PMID:30087334</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6gh4" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] | |||
*[[MHC 3D structures|MHC 3D structures]] | |||
*[[MHC I 3D structures|MHC I 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mycobacteriaceae]] | |||
[[Category: Gillespie GM]] | |||
[[Category: Harlos K]] | |||
[[Category: Jones EY]] | |||
[[Category: McMichael AJ]] | |||
[[Category: Rozbesky D]] | |||
[[Category: Walters LC]] | |||
Latest revision as of 12:58, 23 October 2024
HLA-E*01:03 in complex with the Mtb44 peptide variant: Mtb44*P2-Gln.HLA-E*01:03 in complex with the Mtb44 peptide variant: Mtb44*P2-Gln.
Structural highlights
FunctionHLAE_HUMAN Preferably binds to a peptide derived from the signal sequence of most HLA-A, -B, -C and -G molecules. Publication Abstract from PubMedThrough major histocompatibility complex class Ia leader sequence-derived (VL9) peptide binding and CD94/NKG2 receptor engagement, human leucocyte antigen E (HLA-E) reports cellular health to NK cells. Previous studies demonstrated a strong bias for VL9 binding by HLA-E, a preference subsequently supported by structural analyses. However, Mycobacteria tuberculosis (Mtb) infection and Rhesus cytomegalovirus-vectored SIV vaccinations revealed contexts where HLA-E and the rhesus homologue, Mamu-E, presented diverse pathogen-derived peptides to CD8(+) T cells, respectively. Here we present crystal structures of HLA-E in complex with HIV and Mtb-derived peptides. We show that despite the presence of preferred primary anchor residues, HLA-E-bound peptides can adopt alternative conformations within the peptide binding groove. Furthermore, combined structural and mutagenesis analyses illustrate a greater tolerance for hydrophobic and polar residues in the primary pockets than previously appreciated. Finally, biochemical studies reveal HLA-E peptide binding and exchange characteristics with potential relevance to its alternative antigen presenting function in vivo. Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding.,Walters LC, Harlos K, Brackenridge S, Rozbesky D, Barrett JR, Jain V, Walter TS, O'Callaghan CA, Borrow P, Toebes M, Hansen SG, Sacha J, Abdulhaqq S, Greene JM, Fruh K, Marshall E, Picker LJ, Jones EY, McMichael AJ, Gillespie GM Nat Commun. 2018 Aug 7;9(1):3137. doi: 10.1038/s41467-018-05459-z. PMID:30087334[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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