EMD-23252
CryoEM structure of the HCMV Trimer gHgLgO in complex with neutralizing fabs 13H11 and MSL-109
EMD-23252
Single-particle2.9 Å
Deposition: 07/01/2021Map released: 10/03/2021
Last modified: 23/10/2024
Sample Organism:
Homo sapiens,
Human cytomegalovirus,
Human cytomegalovirus (strain Merlin)
Sample: HCMV Trimer gHgLgO bound to neutralizing fabs 13H11 and MSL-109
Fitted models: 7lbe (Avg. Q-score: 0.542)
Deposition Authors: Kschonsak M, Rouge L
Sample: HCMV Trimer gHgLgO bound to neutralizing fabs 13H11 and MSL-109
Fitted models: 7lbe (Avg. Q-score: 0.542)
Deposition Authors: Kschonsak M, Rouge L
Structures of HCMV Trimer reveal the basis for receptor recognition and cell entry.
Kschonsak M,
Rouge L,
Arthur CP,
Hoangdung H,
Patel N,
Kim I,
Johnson MC 
,
Kraft E,
Rohou AL,
Gill A,
Martinez-Martin N,
Payandeh J,
Ciferri C
(2021) Cell , 184 , 1232
,
Kraft E,
Rohou AL,
Gill A,
Martinez-Martin N,
Payandeh J,
Ciferri C
(2021) Cell , 184 , 1232
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.
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.