Functional implications of the human T-lymphotropic virus type 1 transmembrane glycoprotein helical hairpin structure

Maerz, Anne L., Center, Rob J., Kemp, Bruce E., Kobe, Bostjan and Poumbourios, Pantelis (2000) Functional implications of the human T-lymphotropic virus type 1 transmembrane glycoprotein helical hairpin structure. Journal of Virology, 74 14: 6614-6621. doi:10.1128/JVI.74.14.6614-6621.2000


Author Maerz, Anne L.
Center, Rob J.
Kemp, Bruce E.
Kobe, Bostjan
Poumbourios, Pantelis
Title Functional implications of the human T-lymphotropic virus type 1 transmembrane glycoprotein helical hairpin structure
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
1098-5514
Publication date 2000-07
Year available 2000
Sub-type Article (original research)
DOI 10.1128/JVI.74.14.6614-6621.2000
Open Access Status DOI
Volume 74
Issue 14
Start page 6614
End page 6621
Total pages 8
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Abstract Retrovirus entry into cells follows receptor binding by the surface exposed envelope glycoprotein (Env) subunit (SU), which triggers the membrane fusion activity of the transmembrane (TM) protein. TM protein fragments expressed in the absence of SU adopt helical hairpin structures comprising a central coiled coil, a region of chain reversal containing a disulfide-bonded loop, and a C-terminal segment that packs onto the exterior of the coiled coil in an antiparallel manner. Here we used in vitro mutagenesis to test the functional role of structural elements observed in a model helical hairpin, gp21 of human T-lymphotropic virus type 1. Membrane fusion activity requires the stabilization of the N and C termini of the central coiled coil by a hydrophobic N cap and a small hydrophobic core, respectively. A conserved Gly-Gly hinge motif preceding the disulfide-bonded loop, a salt bridge that stabilizes the chain reversal region, and interactions between the C-terminal segment and the coiled coil are also critical for fusion activity. Our data support a model whereby the chain reversal region transmits a conformational signal from receptor-bound SU to induce the fusion-activated helical hairpin conformation of the TM protein.
Keyword Virology
Maltose-binding Protein
Murine Leukemia-virus
Envelope Glycoprotein
Membrane-fusion
Influenza Hemagglutinin
Crystal-structure
Atomic-structure
Ebola-virus
Hiv-1 Gp41
Precursor Cleavage
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
 
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Created: Mon, 13 Aug 2007, 11:49:23 EST