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==== | ==Cryo-EM structure of the HCMV pentamer bound by Fabs 2-18 and 8I21== | ||
<StructureSection load='7kbb' size='340' side='right'caption='[[7kbb]]' scene=''> | <StructureSection load='7kbb' size='340' side='right'caption='[[7kbb]], [[Resolution|resolution]] 4.02Å' 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'>[[7kbb]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_betaherpesvirus_5 Human betaherpesvirus 5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KBB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KBB 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=7kbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kbb OCA], [https://pdbe.org/7kbb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kbb RCSB], [https://www.ebi.ac.uk/pdbsum/7kbb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kbb ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.02Å</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=7kbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kbb OCA], [https://pdbe.org/7kbb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kbb RCSB], [https://www.ebi.ac.uk/pdbsum/7kbb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kbb ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/UL128_HCMVA UL128_HCMVA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human cytomegalovirus (HCMV) encodes multiple surface glycoprotein complexes to infect a variety of cell types. The HCMV Pentamer, composed of gH, gL, UL128, UL130, and UL131A, enhances entry into epithelial, endothelial, and myeloid cells by interacting with the cell surface receptor neuropilin 2 (NRP2). Despite the critical nature of this interaction, the molecular determinants that govern NRP2 recognition remain unclear. Here, we describe the cryo-EM structure of NRP2 bound to Pentamer. The high-affinity interaction between these proteins is calcium dependent and differs from the canonical carboxyl-terminal arginine (CendR) binding that NRP2 typically uses. We also determine the structures of four neutralizing human antibodies bound to the HCMV Pentamer to define susceptible epitopes. Two of these antibodies compete with NRP2 binding, but the two most potent antibodies recognize a previously unidentified epitope that does not overlap the NRP2-binding site. Collectively, these findings provide a structural basis for HCMV tropism and antibody-mediated neutralization. | |||
Structural basis for HCMV Pentamer recognition by neuropilin 2 and neutralizing antibodies.,Wrapp D, Ye X, Ku Z, Su H, Jones HG, Wang N, Mishra AK, Freed DC, Li F, Tang A, Li L, Jaijyan DK, Zhu H, Wang D, Fu TM, Zhang N, An Z, McLellan JS Sci Adv. 2022 Mar 11;8(10):eabm2546. doi: 10.1126/sciadv.abm2546. Epub 2022 Mar , 11. PMID:35275718<ref>PMID:35275718</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7kbb" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Human betaherpesvirus 5]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: McLellan JS]] | ||
[[Category: Wrapp D]] | |||
Latest revision as of 14:05, 23 October 2024
Cryo-EM structure of the HCMV pentamer bound by Fabs 2-18 and 8I21Cryo-EM structure of the HCMV pentamer bound by Fabs 2-18 and 8I21
Structural highlights
FunctionPublication Abstract from PubMedHuman cytomegalovirus (HCMV) encodes multiple surface glycoprotein complexes to infect a variety of cell types. The HCMV Pentamer, composed of gH, gL, UL128, UL130, and UL131A, enhances entry into epithelial, endothelial, and myeloid cells by interacting with the cell surface receptor neuropilin 2 (NRP2). Despite the critical nature of this interaction, the molecular determinants that govern NRP2 recognition remain unclear. Here, we describe the cryo-EM structure of NRP2 bound to Pentamer. The high-affinity interaction between these proteins is calcium dependent and differs from the canonical carboxyl-terminal arginine (CendR) binding that NRP2 typically uses. We also determine the structures of four neutralizing human antibodies bound to the HCMV Pentamer to define susceptible epitopes. Two of these antibodies compete with NRP2 binding, but the two most potent antibodies recognize a previously unidentified epitope that does not overlap the NRP2-binding site. Collectively, these findings provide a structural basis for HCMV tropism and antibody-mediated neutralization. Structural basis for HCMV Pentamer recognition by neuropilin 2 and neutralizing antibodies.,Wrapp D, Ye X, Ku Z, Su H, Jones HG, Wang N, Mishra AK, Freed DC, Li F, Tang A, Li L, Jaijyan DK, Zhu H, Wang D, Fu TM, Zhang N, An Z, McLellan JS Sci Adv. 2022 Mar 11;8(10):eabm2546. doi: 10.1126/sciadv.abm2546. Epub 2022 Mar , 11. PMID:35275718[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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