title: Heparin binding sites on Ross River virus revealed by electron cryo-microscopy.
abstract: Cell surface glycosaminoglycans play important roles in cell adhesion and viral entry. Laboratory strains of two alphaviruses, Sindbis and Semliki Forest virus, have been shown to utilize heparan sulfate as an attachment receptor, whereas Ross River virus (RRV) does not significantly interact with it. However, a single amino acid substitution at residue 218 in the RRV E2 glycoprotein adapts the virus to heparan sulfate binding and expands the host range of the virus into chicken embryo fibroblasts. Structures of the RRV mutant, E2 N218R, and its complex with heparin were determined through the use of electron cryo-microscopy and image reconstruction methods. Heparin was found to bind at the distal end of the RRV spikes, in a region of the E2 glycoprotein that has been previously implicated in cell-receptor recognition and antibody binding.
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907-2054, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Marintha
authors.initials: M
authors.lastname: Heil
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kuhn
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Baker
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D002460:Cell Line; D002642:Chick Embryo; D006224:Cricetinae; D020285:Cryoelectron Microscopy; D006497:Heparan Sulfate / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007668:Kidney; D008958:Models, Molecular; D011487:Protein Conformation; D012398:Ross River virus / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000648:ultrastructure*
chemical_list: D006497:Heparan Sulfate; D014759:Viral Envelope Proteins