the conserved residue arg46 in the n-terminal heptad repeat domain of hiv-1 gp41 is critical for viral fusion and entry氨基的守恒的残留arg46七个重复域hiv - 1 gp41为病毒融合和条目是至关重要的.pdfVIP

The Conserved Residue Arg46 in the N-Terminal Heptad Repeat Domain of HIV-1 gp41 Is Critical for Viral Fusion and Entry 1. 1. 1. 1 1 2,3 3 Xiaoyi Wang , Weiliang Xiong , Xiaochu Ma , Meili Wei , Yanxia Chen , Lu Lu , Asim K. Debnath , 2,3 1 Shibo Jiang *, Chungen Pan * 1 Key Laboratory of Tropical Disease Control of MOE, Department of Biochemistry and The Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China, 2 Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China, 3 Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America Abstract During the process of HIV-1 fusion with the target cell, the N-terminal heptad repeat (NHR) of gp41 interacts with the C- terminal heptad repeat (CHR) to form fusogenic six-helix bundle (6-HB) core. We previously identified a crucial residue for 6- HB formation and virus entry - Lys63 (K63) in the C-terminal region of NHR (aa 54–70), which forms a hydrophobic cavity. It can form an important salt bridge with Asp121 (D121) in gp41 CHR. Here, we found another important conserved residue for virus fusion and entry, Arg46 (R46), in the N-terminal region of NHR (aa 35–53), which forms a hydrogen bond with a polar residue, Asn43 (N43), in NHR, as a part of the hydrogen-bond network. R46 can also form a salt bridge with a negatively charged residue, Glu137 (E137), in gp41 CHR. Substitution of R46 with the hydrophobic residue Ala (R46A) or the negatively charged residue Glu (R46E) resulted in