7LBE

CryoEM structure of the HCMV Trimer gHgLgO in complex with neutralizing fabs 13H11 and MSL-109

7LBE の概要

• エントリーDOI: 10.2210/pdb7lbe/pdb
• EMDBエントリー: 23252
• 分子名称: Envelope glycoprotein H, 2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose, ... (11 entities in total)
• 機能のキーワード: virus, receptor, complex, neutralizing antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Human cytomegalovirus (strain Merlin) (HHV-5); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 290381.25

構造登録者

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. (登録日: 2021-01-07, 公開日: 2021-03-10, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.9 Å)