Open AccessIdentification of the membrane-spanning domain of glycoprotein 45 in bovine immunodeficiency virus
Author(s) -
Weiping Shen,
Junli Feng,
Z Liu,
Danhong Diao,
C H Liu,
XiangPeng Kong
Publication year - 2018
Publication title -
acta virologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.412
H-Index - 33
eISSN - 1336-2305
pISSN - 0001-723X
DOI - 10.4149/av_2018_223
Subject(s) - gp41 , glycoprotein , lipid bilayer , lipid bilayer fusion , peptide sequence , viral envelope , cell fusion , biology , fusion protein , transmembrane domain , amino acid , biochemistry , microbiology and biotechnology , biophysics , membrane , recombinant dna , cell , gene , genetics , epitope , antigen
The membrane-spanning domain (MSD) of the transmembrane subunit (TM) anchors the envelope glycoprotein (Env) on the lipid bilayer of the host cell membrane and virions. Its functions include membrane fusion efficiency and intracellular trafficking of the lentivirus envelope protein. Our study aimed to determine the MSD of bovine immunodeficiency virus (BIV) glycoprotein 45 (gp45) and reveal structural characteristics of the BIV Env protein. We have predicted the region of the BIV MSD and obtained the sequence using bioinformatics software. Various kinds of assays, including analogy analysis, fluorescence microscopy, and dye-transfer-based assays, were carried out to validate the prediction. The results, for the first time, show that the BIV MSD is located at the D170 to M191 amino acids of gp45, and the identified MSD divides gp45 into the extracellular domain (ED), MSD and cytoplasmic domain (CT). We further found that the BIV MSD had a similar structure and function as the HIV MSD using amino acid sequence alignment and fluorescence microscopy. Additionally, the dye-transfer-based assay demonstrates that deletion of the BIV MSD efficiently decreases cell-cell fusion. Based on the identification of the MSD, a "snorkeling" model, in which the flanking charged amino acid residues are buried in the lipid bilayer while their side chains interact with polar head groups, was proposed for the BIV MSD. Ultimately, we further improved the primary structure of the BIV envelope glycoprotein.