Crystal structure of the conserved herpesvirus fusion regulator complex gH–gL

• Published in: Nature structural & molecular biology Vol. 17; no. 7; pp. 882 - 888
• Main Authors: Chowdary, Tirumala K, Cairns, Tina M, Atanasiu, Doina, Cohen, Gary H, Eisenberg, Roselyn J, Heldwein, Ekaterina E
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2010; Nature Publishing Group
• Subjects: 631/326/596/1553; 631/326/596/2116; 631/535; Animals; Antibodies, Neutralizing - chemistry; Antibodies, Neutralizing - immunology; Biochemistry; Biological Microscopy; Biomedical and Life Sciences; CHO Cells; Conformation; Cricetinae; Cricetulus; Crystal structure; Crystallography, X-Ray; Epitopes - chemistry; Epitopes - immunology; Genetic aspects; Glycoproteins - chemistry; Glycoproteins - immunology; Herpes simplex virus 2; Herpes viruses; Herpesvirus; Herpesvirus 2, Human - chemistry; Herpesvirus 2, Human - immunology; Herpesviruses; Life Sciences; Membrane Biology; Membranes; Models, Molecular; Molecular biology; Physiological aspects; Protein Conformation; Protein Structure; Protein Structure, Tertiary; Proteins; Structure; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - immunology; Viral proteins; United States
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/nsmb.1837

Herpesviruses contain two conserved fusion machinery components, gB and the gH–gL complex. The crystal structure of the gH ectodomain bound to gL from herpes simplex virus 2 forms an unusually tight complex that does not resemble any known fusogen. Instead, it is proposed that gH–gL may activate the fusogenic potential of gB by binding it directly. Herpesviruses, which cause many incurable diseases, infect cells by fusing viral and cellular membranes. Whereas most other enveloped viruses use a single viral catalyst called a fusogen, herpesviruses, inexplicably, require two conserved fusion-machinery components, gB and the heterodimer gH–gL, plus other nonconserved components. gB is a class III viral fusogen, but unlike other members of its class, it does not function alone. We determined the crystal structure of the gH ectodomain bound to gL from herpes simplex virus 2. gH–gL is an unusually tight complex with a unique architecture that, unexpectedly, does not resemble any known viral fusogen. Instead, we propose that gH–gL activates gB for fusion, possibly through direct binding. Formation of a gB–gH–gL complex is critical for fusion and is inhibited by a neutralizing antibody, making the gB–gH–gL interface a promising antiviral target.