Herpes Research Today is a free monthly online journal that collates and summarizes the latest research about Herpes, including details on herpes simplex virus (hsv), genital, oral, symptoms, treatment.

Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry.

Krummenacher C, Supekar VM, Whitbeck JC, Lazear E, Connolly SA, Eisenberg RJ, Cohen GH, Wiley DC, Carfí A

Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.

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.

Published 7 December 2005 in EMBO J, 24(23): 4144-53.
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