Functional implications of the human T-lymphotropic virus type 1 transmembrane glycoprotein helical hairpin structure.
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.
Maerz
A L
AL
St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
Center
R J
RJ
Kemp
B E
BE
Kobe
B
B
Poumbourios
P
P
D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D015686:Gene Products, env / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008561:Membrane Fusion; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D054299:env Gene Products, Human Immunodeficiency Virus
D015686:Gene Products, env; D011993:Recombinant Fusion Proteins; D015682:Retroviridae Proteins, Oncogenic; D054299:env Gene Products, Human Immunodeficiency Virus; C055265:gp21 protein, Human T-lymphotropic virus 1