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Journal of Virology, July 2000, p. 6614-6621, Vol. 74, No. 14
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Functional Implications of the Human T-Lymphotropic Virus Type 1 Transmembrane Glycoprotein Helical Hairpin Structure

Anne L. Maerz, Rob J. Center,dagger Bruce E. Kemp, Bostjan Kobe, and Pantelis Poumbourios*

St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia

Received 13 January 2000/Accepted 17 April 2000

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.

* Corresponding author. Mailing address: St. Vincent's Institute of Medical Research, 41 Victoria Pde, Fitzroy VIC 3065, Australia. Phone: 61-3-9288-2480. Fax: 61-3-9416-2676. E-mail: apoum{at}ariel.its.unimelb.edu.au.

dagger Present address: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.

Journal of Virology, July 2000, p. 6614-6621, Vol. 74, No. 14
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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