Contact residues and predicted structure of the reovirus type 3-receptor interaction.
Sequence similarity between the reovirus type 3 hemagglutinin (HA3) and a anti-idiotypic monoclonal antibody (87.92.6) has been shown to define the site of interaction with a neutralizing (idiotypic) monoclonal antibody (9B.G5) and the cellular receptor for the virus. A synthetic peptide (VL peptide) derived from the anti-idiotypic sequence inhibits viral binding to the receptor. In this study, variants of the VL peptide were utilized to probe specific amino acid residues involved in binding the neutralizing antibody and the receptor. These studies indicate that the--OH groups of several residues are involved in contacting the reovirus type 3 receptor, including Tyr49, Ser50, Ser52, and Thr53 in the anti-idiotypic sequence, corresponding to Tyr326, Ser327, Ser329, and Ser325 in HA3, respectively. In contrast, only Ser50 of the anti-idiotypic sequence, corresponding to Ser327 of HA3, significantly altered neutralizing antibody binding. Additional studies implicate sialic acid as a potential reovirus type 3 receptor on some cells. This includes inhibition of binding of reovirus type 3 and 87.92.6 to L cells by heavily sialylated glycoproteins. Sialic acid was therefore utilized as a candidate receptor to analyze potential interaction schemes with HA3/87.92.6. Sequence similarity to other immunoglobulin structures with similar sequences allowed modeling of the three-dimensional structure of these epitopes. These structures, in combination with peptide studies, allow the development of a model of the interaction of these epitopes with sialic acid, which serves as a reovirus type 3 receptor. These models reveal that similar amino acid residues and side-chain geometries may be utilized by the reovirus type 3 and influenza hemagglutinins in their interactions with cell-surface receptors.
Williams
W V
WV
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia.
Kieber-Emmons
T
T
Weiner
D B
DB
Rubin
D H
DH
Greene
M I
MI
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry; D001667:Binding, Competitive; D003196:Computer Graphics; D000939:Epitopes; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D007739:L Cells; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000494:pharmacology; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism* / Q000648:ultrastructure; D012087:Reoviridae / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D012794:Sialic Acids / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism
D000956:Antigens, Viral; D000939:Epitopes; D006389:Hemagglutinins, Viral; D009842:Oligopeptides; D010446:Peptide Fragments; D011991:Receptors, Virus; D012794:Sialic Acids; D012795:Sialoglycoproteins; D009439:Neuraminidase