2C36

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

2C36 の概要

• エントリーDOI: 10.2210/pdb2c36/pdb
• 関連するPDBエントリー: 1JMA 1L2G 2C3A
• 分子名称: 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)
• 機能のキーワード: virus, viral protein, herpes, immunoglobulin-like, glycoprotein, transmembrane
• 由来する生物種: HUMAN HERPESVIRUS 1 (HERPES SIMPLEX VIRUS (HSV-1, HUMAN))
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65049.04

構造登録者

Krummenacher, C.,Supekar, V.M.,Whitbeck, J.C.,Lazear, E.,Connolly, S.A.,Eisenberg, R.J.,Cohen, G.H.,Wiley, D.C.,Carfi, A. (登録日: 2005-10-04, 公開日: 2005-11-23, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.11 Å)