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Basic Characteristics of Mutations
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Mutation Site
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R222A |
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Mutation Site Sentence
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In particular, the side chain of Arg222 of gD is in salt bridge distance of nectin-1 Glu125 ( Fig. 2A ) consistent with the decrease in gD/Nectin-1 binding affinity seen when Arg222 was mutated to alanine [45] , [46]. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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gD |
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Standardized Encoding Gene
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US6
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Herpes simplex
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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21980294
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Title
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Structure of herpes simplex virus glycoprotein D bound to the human receptor nectin-1
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Author
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Di Giovine P,Settembre EC,Bhargava AK,Luftig MA,Lou H,Cohen GH,Eisenberg RJ,Krummenacher C,Carfi A
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Journal
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PLoS pathogens
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Journal Info
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2011 Sep;7(9):e1002277
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Abstract
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Binding of herpes simplex virus (HSV) glycoprotein D (gD) to a cell surface receptor is required to trigger membrane fusion during entry into host cells. Nectin-1 is a cell adhesion molecule and the main HSV receptor in neurons and epithelial cells. We report the structure of gD bound to nectin-1 determined by x-ray crystallography to 4.0 A resolution. The structure reveals that the nectin-1 binding site on gD differs from the binding site of the HVEM receptor. A surface on the first Ig-domain of nectin-1, which mediates homophilic interactions of Ig-like cell adhesion molecules, buries an area composed by residues from both the gD N- and C-terminal extensions. Phenylalanine 129, at the tip of the loop connecting beta-strands F and G of nectin-1, protrudes into a groove on gD, which is otherwise occupied by C-terminal residues in the unliganded gD and by N-terminal residues in the gD/HVEM complex. Notably, mutation of Phe129 to alanine prevents nectin-1 binding to gD and HSV entry. Together these data are consistent with previous studies showing that gD disrupts the normal nectin-1 homophilic interactions. Furthermore, the structure of the complex supports a model in which gD-receptor binding triggers HSV entry through receptor-mediated displacement of the gD C-terminal region.
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Sequence Data
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-
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