2XZ3

BLV TM hairpin

2XZ3 の概要

• エントリーDOI: 10.2210/pdb2xz3/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900001
• 分子名称: MALTOSE ABC TRANSPORTER PERIPLASMIC PROTEIN, ENVELOPE GLYCOPROTEIN, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: viral protein, viral membrane fusion, hairpin, chimera
• 由来する生物種: ESCHERICHIA COLI; 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 51964.21

構造登録者

Schuettelkopf, A.W.,Lamb, D.,Brighty, D.W.,van Aalten, D.M.F. (登録日: 2010-11-22, 公開日: 2011-03-02, 最終更新日: 2023-12-20)

主引用文献

Lamb, D.,Schuttelkopf, A.W.,Van Aalten, D.M.F.,Brighty, D.W.
Charge-Surrounded Pockets and Electrostatic Interactions with Small Ions Modulate the Activity of Retroviral Fusion Proteins.
Plos Pathog., 7:1268-, 2011

PubMed Abstract: Refolding of viral class-1 membrane fusion proteins from a native state to a trimer-of-hairpins structure promotes entry of viruses into cells. Here we present the structure of the bovine leukaemia virus transmembrane glycoprotein (TM) and identify a group of asparagine residues at the membrane-distal end of the trimer-of-hairpins that is strikingly conserved among divergent viruses. These asparagines are not essential for surface display of pre-fusogenic envelope. Instead, substitution of these residues dramatically disrupts membrane fusion. Our data indicate that, through electrostatic interactions with a chloride ion, the asparagine residues promote assembly and profoundly stabilize the fusion-active structures that are required for viral envelope-mediated membrane fusion. Moreover, the BLV TM structure also reveals a charge-surrounded hydrophobic pocket on the central coiled coil and interactions with basic residues that cluster around this pocket are critical to membrane fusion and form a target for peptide inhibitors of envelope function. Charge-surrounded pockets and electrostatic interactions with small ions are common among class-1 fusion proteins, suggesting that small molecules that specifically target such motifs should prevent assembly of the trimer-of-hairpins and be of value as therapeutic inhibitors of viral entry.

PubMed: 21304939
DOI: 10.1371/JOURNAL.PPAT.1001268

実験手法

X-RAY DIFFRACTION (1.95 Å)