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Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1
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 de...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182920/ https://www.ncbi.nlm.nih.gov/pubmed/21980294 http://dx.doi.org/10.1371/journal.ppat.1002277 |
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author | Di Giovine, Paolo Settembre, Ethan C. Bhargava, Arjun K. Luftig, Micah A. Lou, Huan Cohen, Gary H. Eisenberg, Roselyn J. Krummenacher, Claude Carfi, Andrea |
author_facet | Di Giovine, Paolo Settembre, Ethan C. Bhargava, Arjun K. Luftig, Micah A. Lou, Huan Cohen, Gary H. Eisenberg, Roselyn J. Krummenacher, Claude Carfi, Andrea |
author_sort | Di Giovine, Paolo |
collection | PubMed |
description | 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 Å 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 β-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. |
format | Online Article Text |
id | pubmed-3182920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31829202011-10-06 Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1 Di Giovine, Paolo Settembre, Ethan C. Bhargava, Arjun K. Luftig, Micah A. Lou, Huan Cohen, Gary H. Eisenberg, Roselyn J. Krummenacher, Claude Carfi, Andrea PLoS Pathog Research Article 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 Å 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 β-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. Public Library of Science 2011-09-29 /pmc/articles/PMC3182920/ /pubmed/21980294 http://dx.doi.org/10.1371/journal.ppat.1002277 Text en Di Giovine et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Di Giovine, Paolo Settembre, Ethan C. Bhargava, Arjun K. Luftig, Micah A. Lou, Huan Cohen, Gary H. Eisenberg, Roselyn J. Krummenacher, Claude Carfi, Andrea Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1 |
title | Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1 |
title_full | Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1 |
title_fullStr | Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1 |
title_full_unstemmed | Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1 |
title_short | Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1 |
title_sort | structure of herpes simplex virus glycoprotein d bound to the human receptor nectin-1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182920/ https://www.ncbi.nlm.nih.gov/pubmed/21980294 http://dx.doi.org/10.1371/journal.ppat.1002277 |
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