Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

The Pro-Fusion Domain of Herpes Simplex Virus Glycoprotein D (gD) Interacts with the gD N Terminus and Is Displaced by Soluble Forms of Viral Receptors

Daniela Fusco, Cristina Forghieri, Gabriella Campadelli-Fiume and Bernard Roizman
Proceedings of the National Academy of Sciences of the United States of America
Vol. 102, No. 26 (Jun. 28, 2005), pp. 9323-9328
Stable URL: http://www.jstor.org/stable/3375894
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
The Pro-Fusion Domain of Herpes Simplex Virus Glycoprotein D (gD) Interacts with the gD N Terminus and Is Displaced by Soluble Forms of Viral Receptors
Preview not available

Abstract

Entry of herpes simplex virus into the cell requires the interaction of gD with one of its receptors, herpesvirus entry mediator or nectin 1, and the intervention of gB, gH, or gL, required to execute fusion of the virion envelope with cell membranes. The gD ectodomain is organized in two structurally and functionally differentiated regions. The N terminus (residues 1-260) carries the receptor binding sites, and the C terminus (residues 260-310) functions as the pro-fusion domain (PFD), which is required for viral infectivity and fusion but not for receptor binding. The objective of our studies is to elucidate how gD links receptor recognition to the triggering of fusion. Here, we show that PFD is made of subdomains 1 and 2 (amino acids 260-285 and 285-310). Each one partially contributed to herpes simplex virus infectivity. By means of glutathione S-transferase (GST) fusion proteins, we show that PFD bound soluble forms of gD, truncated at residue 260 ( gD260 t) or downstream. Both PFD subdomains bound gD260 t, highlighting multiple contact sites between the N and C termini of gD. When gD260 t was in complex with either receptor, it failed to bind GST-PFD. In turn, the receptors did not bind GST-PFD, irrespective of whether they were in complex with gD. Thus, gD260 t interacted with the C terminus only if unbound to the receptor. We propose that (i) before receptor binding, gD adopts a "closed" conformation in which the N and C termini interact; and (ii) on encounter with a receptor, gD modifies its conformation and the N and C termini are released from reciprocal interactions ("opened" conformation) and enabled to trigger fusion.

Page Thumbnails

  • Thumbnail: Page 
[9323]
    [9323]
  • Thumbnail: Page 
9324
    9324
  • Thumbnail: Page 
9325
    9325
  • Thumbnail: Page 
9326
    9326
  • Thumbnail: Page 
9327
    9327
  • Thumbnail: Page 
9328
    9328