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==== | ==3H4-Fab HLA-E-VL9 co-complex== | ||
<StructureSection load='7bh8' size='340' side='right'caption='[[7bh8]]' scene=''> | <StructureSection load='7bh8' size='340' side='right'caption='[[7bh8]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7bh8]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BH8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BH8 FirstGlance]. <br> | ||
</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=7bh8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bh8 OCA], [https://pdbe.org/7bh8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bh8 RCSB], [https://www.ebi.ac.uk/pdbsum/7bh8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bh8 ProSAT]</span></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]] 1.8Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7bh8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bh8 OCA], [https://pdbe.org/7bh8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bh8 RCSB], [https://www.ebi.ac.uk/pdbsum/7bh8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bh8 ProSAT]</span></td></tr> | |||
</table> | </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 == | |||
The non-classical class Ib molecule human leukocyte antigen E (HLA-E) has limited polymorphism and can bind HLA class Ia leader peptides (VL9). HLA-E-VL9 complexes interact with the natural killer (NK) cell receptors NKG2A-C/CD94 and regulate NK cell-mediated cytotoxicity. Here we report the isolation of 3H4, a murine HLA-E-VL9-specific IgM antibody that enhances killing of HLA-E-VL9-expressing cells by an NKG2A(+) NK cell line. Structural analysis reveal that 3H4 acts by preventing CD94/NKG2A docking on HLA-E-VL9. Upon in vitro maturation, an affinity-optimized IgG form of 3H4 showes enhanced NK killing of HLA-E-VL9-expressing cells. HLA-E-VL9-specific IgM antibodies similar in function to 3H4 are also isolated from naive B cells of cytomegalovirus (CMV)-negative, healthy humans. Thus, HLA-E-VL9-targeting mouse and human antibodies isolated from the naive B cell antibody pool have the capacity to enhance NK cell cytotoxicity. | |||
Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity.,Li D, Brackenridge S, Walters LC, Swanson O, Harlos K, Rozbesky D, Cain DW, Wiehe K, Scearce RM, Barr M, Mu Z, Parks R, Quastel M, Edwards RJ, Wang Y, Rountree W, Saunders KO, Ferrari G, Borrow P, Jones EY, Alam SM, Azoitei ML, Gillespie GM, McMichael AJ, Haynes BF Commun Biol. 2022 Mar 28;5(1):271. doi: 10.1038/s42003-022-03183-5. PMID:35347236<ref>PMID:35347236</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7bh8" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[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__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Rozbesky D]] | |||
[[Category: Walters LC]] | |||
Latest revision as of 15:28, 1 February 2024
3H4-Fab HLA-E-VL9 co-complex3H4-Fab HLA-E-VL9 co-complex
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 PubMedThe non-classical class Ib molecule human leukocyte antigen E (HLA-E) has limited polymorphism and can bind HLA class Ia leader peptides (VL9). HLA-E-VL9 complexes interact with the natural killer (NK) cell receptors NKG2A-C/CD94 and regulate NK cell-mediated cytotoxicity. Here we report the isolation of 3H4, a murine HLA-E-VL9-specific IgM antibody that enhances killing of HLA-E-VL9-expressing cells by an NKG2A(+) NK cell line. Structural analysis reveal that 3H4 acts by preventing CD94/NKG2A docking on HLA-E-VL9. Upon in vitro maturation, an affinity-optimized IgG form of 3H4 showes enhanced NK killing of HLA-E-VL9-expressing cells. HLA-E-VL9-specific IgM antibodies similar in function to 3H4 are also isolated from naive B cells of cytomegalovirus (CMV)-negative, healthy humans. Thus, HLA-E-VL9-targeting mouse and human antibodies isolated from the naive B cell antibody pool have the capacity to enhance NK cell cytotoxicity. Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity.,Li D, Brackenridge S, Walters LC, Swanson O, Harlos K, Rozbesky D, Cain DW, Wiehe K, Scearce RM, Barr M, Mu Z, Parks R, Quastel M, Edwards RJ, Wang Y, Rountree W, Saunders KO, Ferrari G, Borrow P, Jones EY, Alam SM, Azoitei ML, Gillespie GM, McMichael AJ, Haynes BF Commun Biol. 2022 Mar 28;5(1):271. doi: 10.1038/s42003-022-03183-5. PMID:35347236[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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