7LBF

CryoEM structure of the HCMV Trimer gHgLgO in complex with human Platelet-derived growth factor receptor alpha and neutralizing fabs 13H11 and MSL-109

Summary for 7LBF

• Entry DOI: 10.2210/pdb7lbf/pdb
• EMDB information: 23253
• Descriptor: Envelope glycoprotein H, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• Functional Keywords: virus, receptor, complex, neutralizing antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human cytomegalovirus (strain Merlin) (HHV-5); More
• Total number of polymer chains: 8
• Total formula weight: 349960.31

Authors

Kschonsak, M.,Rouge, L.,Arthur, C.P.,Hoangdung, H.,Patel, N.,Kim, I.,Johnson, M.,Kraft, E.,Rohou, A.L.,Gill, A.,Martinez-Martin, N.,Payandeh, J.,Ciferri, C. (deposition date: 2021-01-07, release date: 2021-03-10, Last modification date: 2024-11-20)

Primary citation

Kschonsak, M.,Rouge, L.,Arthur, C.P.,Hoangdung, H.,Patel, N.,Kim, I.,Johnson, M.C.,Kraft, E.,Rohou, A.L.,Gill, A.,Martinez-Martin, N.,Payandeh, J.,Ciferri, C.
Structures of HCMV Trimer reveal the basis for receptor recognition and cell entry.
Cell, 184:1232-, 2021

PubMed Abstract: Human cytomegalovirus (HCMV) infects the majority of the human population and represents the leading viral cause of congenital birth defects. HCMV utilizes the glycoproteins gHgLgO (Trimer) to bind to platelet-derived growth factor receptor alpha (PDGFRα) and transforming growth factor beta receptor 3 (TGFβR3) to gain entry into multiple cell types. This complex is targeted by potent neutralizing antibodies and represents an important candidate for therapeutics against HCMV. Here, we determine three cryogenic electron microscopy (cryo-EM) structures of the trimer and the details of its interactions with four binding partners: the receptor proteins PDGFRα and TGFβR3 as well as two broadly neutralizing antibodies. Trimer binding to PDGFRα and TGFβR3 is mutually exclusive, suggesting that they function as independent entry receptors. In addition, Trimer-PDGFRα interaction has an inhibitory effect on PDGFRα signaling. Our results provide a framework for understanding HCMV receptor engagement, neutralization, and the development of anti-viral strategies against HCMV.

PubMed: 33626330
DOI: 10.1016/j.cell.2021.01.036

Experimental method

ELECTRON MICROSCOPY (2.8 Å)