title: Herpes B virus gD interaction with its human receptor--an in silico analysis approach.
abstract: BACKGROUND
  The glycoprotein D (gD) is essential for Herpes B virus (BV) entry into mammalian cells. Nectin-1, an HSV-1 gD receptor, is found to be the receptor which mediated BV induced cell-cell fusion, while HVEM does not mediate fusion by BV glycoprotein. However, the specific sequence and structural requirements of the BV gD for the recognition of and binding to Nectin-1 are unknown. Moreover, the 3D structures of BV gD and the BV gD-receptor complex have not been determined. In this study, we propose a reliable model of the interaction of the BV gD with receptor using bioinformatics tools.
  
  
  RESULTS
  The three-dimensional structures of two BV gD-receptor complexes were constructed using homology modelling and docking strategy. Based on the models of these complexes, the BV gD receptor interaction patterns were calculated. The results showed that the interface between the BV gD and nectin-1 molecule is not geometrically complementary. The computed molecular interactions indicated that two terminal extensions were the main region of BV gD that binds to nectin-1 and that hydrophobic contacts between the two molecules play key roles in their recognition and binding. The constructed BV gD-HVEM complex model showed that this complex had a lower shape complementarity value and a smaller interface area compared with the HSV-1 gD-HVEM complex, and the number of intermolecular interactions between BV gD-HVEM were fewer than that of HSV-1 gD-HVEM complex. These results could explain why HVEM does not function as a receptor for BV gD.
  
  
  CONCLUSIONS
  In this study, we present structural model for the BV gD in a complex with its receptor. Some features predicted by this model can explain previously reported experimental data. This complex model may lead to a better understanding of the function of BV gD and its interaction with receptor and will improve our understanding of the activation of the BV fusion and entry process.
authors.forename: Lingke
authors.initials: L
authors.lastname: Li
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Qiu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Liang
authors.forename: Huahu
authors.initials: H
authors.lastname: Ye
authors.forename: Yongqin
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Hospital No,307 of PLA, the Academy of Military Medical Sciences, Beijing 100071, China. guowanfeng@hotmail.com.
authors.forename: Wanfeng
authors.initials: W
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Junjie
authors.initials: J
authors.lastname: Yue
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D003198:Computer Simulation; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D000882:Haplorhini; D006568:Herpesvirus 1, Cercopithecine / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000075983:Nectins; D011485:Protein Binding; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D013816:Thermodynamics; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D015815:Cell Adhesion Molecules; D006023:Glycoproteins; C000619010:NECTIN1 protein, human; D000075983:Nectins; D014764:Viral Proteins