2XZ3

BLV TM hairpin

Summary for 2XZ3

• Entry DOI: 10.2210/pdb2xz3/pdb
• Related PRD ID: PRD_900001
• Descriptor: MALTOSE ABC TRANSPORTER PERIPLASMIC PROTEIN, ENVELOPE GLYCOPROTEIN, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: viral protein, viral membrane fusion, hairpin, chimera
• Biological source: ESCHERICHIA COLI; More
• Total number of polymer chains: 1
• Total formula weight: 51964.21

Authors

Schuettelkopf, A.W.,Lamb, D.,Brighty, D.W.,van Aalten, D.M.F. (deposition date: 2010-11-22, release date: 2011-03-02, Last modification date: 2023-12-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.95 Å)