Crystal structure of the conserved herpesvirus fusion regulator complex gH-gL.
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.
Chowdary
Tirumala K
TK
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.
Cairns
Tina M
TM
Atanasiu
Doina
D
Cohen
Gary H
GH
Eisenberg
Roselyn J
RJ
Heldwein
Ekaterina E
EE
D000818:Animals; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006023:Glycoproteins / Q000737:chemistry* / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000737:chemistry* / Q000276:immunology; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology
D057134:Antibodies, Neutralizing; D000939:Epitopes; D006023:Glycoproteins; D014759:Viral Envelope Proteins