Localization of the labile disulfide bond between SU and TM of the murine leukemia virus envelope protein complex to a highly conserved CWLC motif in SU that resembles the active-site sequence of thiol-disulfide exchange enzymes.
Previous studies have indicated that the surface (SU) and transmembrane (TM) subunits of the envelope protein (Env) of murine leukemia viruses (MuLVs) are joined by a labile disulfide bond that can be stabilized by treatment of virions with thiol-specific reagents. In the present study this observation was extended to the Envs of additional classes of MuLV, and the cysteines of SU involved in this linkage were mapped by proteolytic fragmentation analyses to the CWLC sequence present at the beginning of the C-terminal domain of SU. This sequence is highly conserved across a broad range of distantly related retroviruses and resembles the CXXC motif present at the active site of thiol-disulfide exchange enzymes. A model is proposed in which rearrangements of the SU-TM intersubunit disulfide linkage, mediated by the CWLC sequence, play roles in the assembly and function of the Env complex.
Pinter
A
A
Public Health Research Institute, and Department of Microbiology, New York University School of Medicine, New York 10016, USA. pinter@phri.nyu.edu
Kopelman
R
R
Li
Z
Z
Kayman
S C
SC
Sanders
D A
DA
D000818:Animals; D001665:Binding Sites; D003545:Cysteine; D004220:Disulfides; D005622:Friend murine leukemia virus / Q000378:metabolism; D015686:Gene Products, env / Q000737:chemistry* / Q000378:metabolism*; D015752:Genes, env; D007535:Isomerases / Q000737:chemistry* / Q000378:metabolism; D016350:Leucine Zippers; D009052:Leukemia Virus, Murine / Q000378:metabolism*; D051379:Mice; D008979:Moloney murine leukemia virus / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry; D019704:Protein Disulfide-Isomerases
D004220:Disulfides; D015686:Gene Products, env; D010446:Peptide Fragments; D007535:Isomerases; D019704:Protein Disulfide-Isomerases; D003545:Cysteine