2C36

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

Summary for 2C36

• Entry DOI: 10.2210/pdb2c36/pdb
• Related: 1JMA 1L2G 2C3A
• Descriptor: GLYCOPROTEIN D HSV-1, alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: virus, viral protein, herpes, immunoglobulin-like, glycoprotein, transmembrane
• Biological source: HUMAN HERPESVIRUS 1 (HERPES SIMPLEX VIRUS (HSV-1, HUMAN))
• Total number of polymer chains: 2
• Total formula weight: 65049.04

Authors

Krummenacher, C.,Supekar, V.M.,Whitbeck, J.C.,Lazear, E.,Connolly, S.A.,Eisenberg, R.J.,Cohen, G.H.,Wiley, D.C.,Carfi, A. (deposition date: 2005-10-04, release date: 2005-11-23, Last modification date: 2024-11-20)

Primary citation

Krummenacher, C.,Supekar, V.M.,Whitbeck, J.C.,Lazear, E.,Connolly, S.A.,Eisenberg, R.J.,Cohen, G.H.,Wiley, D.C.,Carfi, A.
Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry.
EMBO J., 24:4144-4153, 2005

PubMed 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.

PubMed: 16292345
DOI: 10.1038/sj.emboj.7600875

Experimental method

X-RAY DIFFRACTION (2.11 Å)