Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: The membrane-spanning domain of gp41 plays a critical role in intracellular trafficking of the HIV envelope protein. | Miyauchi et al. Retrovirology 2010 7 95 http content 7 1 95 RETR0VIR0L0GY RESEARCH Open Access The membrane-spanning domain of gp41 plays a critical role in intracellular trafficking of the HIV envelope protein Kosuke Miyauchi1 A Rachael Curran2 Yufei Long3 Naoyuki Kondo3 5 6 Aikichi Iwamoto4 Donald M Engelman2 Zene Matsuda3 5 Abstract Background The sequences of membrane-spanning domains MSDs on the gp41 subunit are highly conserved among many isolates of HIV-1. The GXXXG motif a potential helix-helix interaction motif and an arginine residue rare in hydrophobic MSDs are especially well conserved. These two conserved elements are expected to locate on the opposite sides of the MSD if the MSD takes a a-helical secondary structure. A scanning alanine-insertion mutagenesis was performed to elucidate the structure-function relationship of gp41 MSD. Results A circular dichroism analysis of a synthetic gp41 MSD peptide determined that the secondary structure of the gp41 MSD was a-helical. We then performed a scanning alanine-insertion mutagenesis of the entire gp41 MSD progressively shifting the relative positions of MSD segments around the helix axis. Altering the position of Gly694 the last residue of the GXXXG motif relative to Arg696 the number indicates the position of the amino acid residues in HXB2 Env around the axis resulted in defective fusion. These mutants showed impaired processing of the gp160 precursor into gp120 and gp41. Furthermore these Env mutants manifested inefficient intracellular transport in the endoplasmic reticulum and Golgi regions. Indeed a transplantation of the gp41 MSD portion into the transmembrane domain of another membrane protein Tac altered its intracellular distribution. Our data suggest that the intact MSD a-helix is critical in the intracellular trafficking of HIV-1 Env. Conclusions The relative position between the highly conserved GXXXG motif and an arginine residue around the gp41 MSD a-helix is critical .
