4.4 Article

Induction of conformational changes at the N-terminus of herpes simplex virus glycoprotein D upon binding to HVEM and nectin-1

Journal

VIROLOGY
Volume 448, Issue -, Pages 185-195

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2013.10.019

Keywords

Herpes simplex virus; Receptors; Nectin; HVEM; Glycoproteins; Structure; Virus entry

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Funding

  1. Public Health Service grant from the National Institute of Allergy and Infectious Diseases [AI-097171, AI-073384, AI-056045, AI-076231, AI-018289]

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Herpes simplex virus entry is initiated by glycoprotein D (gD) binding to a cellular receptor, such as HVEM or nectin-1. gD is activated by receptor-induced displacement of the C-terminus from the core of the glycoprotein. Binding of HVEM requires the formation of an N-terminal hairpin loop of gD; once formed this loop masks the nectin-1 binding site on the core of gD. We found that HVEM and nectin-1 exhibit non-reciprocal competition for binding to gD. The N-terminus of gD does not spontaneously form a stable hairpin in the absence of receptor and HVEM does not appear to rely on a pre-existing hairpin for binding to gD(3C-38C) mutants. However, HVEM function is affected by mutations that impair optimal hairpin formation. Furthermore, nectin-1 induces a new conformation of the N-terminus of gD. We conclude that the conformation of the N-terminus of gD is actively modified by the direct action of both receptors. (C) 2013 Elsevier Inc. All rights reserved.

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