title: Binding of herpes simplex virus glycoprotein D to nectin-1 exploits host cell adhesion.
abstract: Multiple surface envelope proteins are involved in the human herpes simplex virus type 1 entry and fusion. Among them, glycoprotein D (gD) has an important role by binding to the host receptors such as herpes virus entry mediator and nectin-1. Although the complex structure of gD with herpes virus entry mediator has been established, the binding mode of gD with the nectin-1 is elusive. Nectin-1 is a member of the immunoglobulin (Ig)-like (three Ig-like domains) cell adhesion molecules and is believed to form a homodimer to exert its functions. Here we report the complex structure of gD and nectin-1 (three Ig domains), revealing that gD binds the first Ig domain of nectin-1 in a similar mode to the nectin-1 homodimer interaction. The key amino acids responsible for nectin-1 dimerization are also used for gD/nectin-1 binding. This result indicates that binding of gD to nectin-1 would preclude the nectin-1 dimerization, consequently abolishing its cell adhesion function.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beichen West Road, Beijing 100101, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
authors.forename: Guangwen
authors.initials: G
authors.lastname: Lu
authors.forename: Zhengfei
authors.initials: Z
authors.lastname: Guo
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fan
authors.forename: Jiawei
authors.initials: J
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.forename: Jianxun
authors.initials: J
authors.lastname: Qi
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D016367:Baculoviridae; D001665:Binding Sites; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D019281:Dimerization; D004926:Escherichia coli; D006561:Herpes Simplex / Q000378:metabolism* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D000075983:Nectins; D010957:Plasmids; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; D000075983:Nectins; D011991:Receptors, Virus; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1