An N-terminal glycine-rich sequence contributes to retrovirus trimer of hairpins stability.
Retroviral transmembrane proteins (TMs) contain a glycine-rich segment linking the N-terminal fusion peptide and coiled coil core. Previously, we reported that the glycine-rich segment (Met-326-Ser-337) of the human T-cell leukemia virus type 1 (HTLV-1) TM, gp21, is a determinant of membrane fusion function [K.A. Wilson, S. Bär, A.L. Maerz, M. Alizon, P. Poumbourios, 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, J. Virol. 79 (2005) 4533-4539]. Here we show that the reduced fusion activity of an I334A mutant correlated with a decrease in stability of the gp21 trimer of hairpins conformation, in the context of a maltose-binding protein-gp21 chimera. The stabilizing influence of Ile-334 required the C-terminal membrane-proximal sequence Trp-431-Ser-436. Proline substitution of four of five Gly residues altered gp21 trimer of hairpins stability. Our data indicate that flexibility within and hydrophobic interactions mediated by this region are determinants of gp21 stability and membrane fusion function.
Wilson
Kirilee A
KA
St. Vincent's Institute of Medical Research, VIC 3065, Australia.
Maerz
Anne L
AL
Bär
Séverine
S
Drummer
Heidi E
HE
Poumbourios
Pantelis
P
D000595:Amino Acid Sequence; D004355:Drug Stability; D015686:Gene Products, env / Q000737:chemistry*; D005998:Glycine / Q000737:chemistry*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012190:Retroviridae / Q000737:chemistry*; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry*; D013329:Structure-Activity Relationship; 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; D005998:Glycine