We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry.
- Authors
Krummenacher, Claude; Supekar, Vinit M; Whitbeck, J Charles; Lazear, Eric; Connolly, Sarah A; Eisenberg, Roselyn J; Cohen, Gary H; Wiley, Don C; Carfí, Andrea
- Abstract
Herpes simplex virus (HSV) entry into cells requires binding of the envelope glycoprotein D (gD) to one of several cell surface receptors. The 50 C-terminal residues of the gD ectodomain are essential for virus entry, but not for receptor binding. We have determined the structure of an unliganded gD molecule that includes these C-terminal residues. The structure reveals that the C-terminus is anchored near the N-terminal region and masks receptor-binding sites. Locking the C-terminus in the position observed in the crystals by an intramolecular disulfide bond abolished receptor binding and virus entry, demonstrating that this region of gD moves upon receptor binding. Similarly, a point mutant that would destabilize the C-terminus structure was nonfunctional for entry, despite increased affinity for receptors. We propose that a controlled displacement of the gD C-terminus upon receptor binding is an essential feature of HSV entry, ensuring the timely activation of membrane fusion.
- Subjects
MEDICAL sciences; HERPES simplex virus; HERPESVIRUSES; VIRUSES; HERPESVIRUS diseases; CELL membranes; SKIN infections; IMMUNOSPECIFICITY; BINDING sites; MOLECULES; MEMBRANE fusion
- Publication
EMBO Journal, 2005, Vol 24, Issue 23, p4144
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/sj.emboj.7600875