title: The receptor-binding domain of pseudorabies virus glycoprotein gC is composed of multiple discrete units that are functionally redundant.
abstract: Many herpesviruses attach to cells in a two-step process, using the glycoprotein gC family of homologs to bind the primary receptor, heparan sulfate (HS) proteoglycan, and glycoprotein gD homologs to bind an unknown secondary receptor. We have previously shown by deletion analysis that the amino-terminal one-third of gC from pseudorabies virus (PRV), a swine herpesvirus, includes at least the principal HS receptor-binding domain. This portion of PRV gC contains three discrete clusters of basic residues that exactly or nearly match proposed consensus sequences for heparin-binding domains (HBDs); four additional potential HBDs lie in the distal two-thirds of the glycoprotein. We now specifically implicate each of the three amino-terminal HBDs in virus attachment. Mutational analysis demonstrated that any one of the three HBDs could mediate efficient virus infectivity; HS-dependent PRV attachment to cells was eliminated only after all three amino-terminal HBDs were altered. Furthermore, the binding dysfunction was due to a disruption of the specific HBDs and not to total charge loss. Thus, unlike previously described viral receptor-binding domains, the PRV gC receptor-binding domain is composed of multiple, discrete units that can function independently of one another. These units may function redundantly either to increase binding affinity or perhaps to effectively increase the virus's host range.
authors.affiliation: Department of Microbiology and Immunology, University of Tennessee at Memphis, Memphis 38163, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Flynn
authors.forename: P
authors.initials: P
authors.lastname: Ryan
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D004563:Electrochemistry; D006493:Heparin / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism*; D011558:Herpesvirus 1, Suid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D006493:Heparin; D006497:Heparan Sulfate; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C042966:pseudorabies virus glycoproteins