The conserved glycine-rich segment linking the N-terminal fusion peptide to the coiled coil of human T-cell leukemia virus type 1 transmembrane glycoprotein gp21 is a determinant of membrane fusion function.
Retroviral transmembrane proteins (TMs) contain an N-terminal fusion peptide that initiates virus-cell membrane fusion. The fusion peptide is linked to the coiled-coil core through a conserved sequence that is often rich in glycines. We investigated the functional role of the glycine-rich segment, Met-326 to Ser-337, of the human T-cell leukemia virus type 1 (HTLV-1) TM, gp21, by alanine and proline scanning mutagenesis. Alanine substitution for the hydrophobic residue Ile-334 caused an approximately 90% reduction in cell-cell fusion activity without detectable effects on the lipid-mixing and pore formation phases of fusion. Alanine substitutions at other positions had smaller effects (Gly-329, Val-330, and Gly-332) or no effect on fusion function. Proline substitution for glycine residues inhibited cell-cell fusion function with position-dependent effects on the three phases of fusion. Retroviral glycoprotein fusion function thus appears to require flexibility within the glycine-rich segment and hydrophobic contacts mediated by this segment.
Wilson
Kirilee A
KA
St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
Bär
Séverine
S
Maerz
Anne L
AL
Alizon
Marc
M
Poumbourios
Pantelis
P
D019943:Amino Acid Substitution; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D008561:Membrane Fusion; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D017434:Protein Structure, Tertiary; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D054299:env Gene Products, Human Immunodeficiency Virus
D015686:Gene Products, env; D015682:Retroviridae Proteins, Oncogenic; D054299:env Gene Products, Human Immunodeficiency Virus; C055265:gp21 protein, Human T-lymphotropic virus 1