title: P20A inhibits HIV-1 fusion through its electrostatic interaction with the distal region of the gp41 fusion core.
abstract: We previously identified an HIV-1 fusion inhibitor P20A targeting HIV-1 gp41 6-HB fusion core. Using alanine scanning mutagenesis, we investigated the effect of 6-HB surface residue mutations on the binding affinity between P20A and 6-HB. Substitution of positively or negatively charged residues in the distal region of 6-HB with alanines resulted in significant decrease or increase of its binding affinity to P20A, respectively. The 6-HB with E630K, D632K, or E634K mutation exhibited enhanced binding affinity with P20A, suggesting that P20A blocks HIV-1 fusion through electrostatic interaction with the positively charged residues in the distal region of the gp41 fusion core.
authors.affiliation: Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, Protein Science Laboratory of the Ministry of Education, Beijing 100084, China.
authors.forename: Shushu
authors.initials: S
authors.lastname: Fu
authors.affiliation: Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, Protein Science Laboratory of the Ministry of Education, Beijing 100084, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Tong
authors.affiliation: Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, Protein Science Laboratory of the Ministry of Education, Beijing 100084, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tan
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: zhuyun@moon.ibp.ac.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, Protein Science Laboratory of the Ministry of Education, Beijing 100084, China. Electronic address: chenyh@mail.tsinghua.edu.cn.
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D023581:HIV Fusion Inhibitors / Q000737:chemistry* / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D016415:Sequence Alignment; D055672:Static Electricity; D053586:Virus Internalization
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors
keywords: Alanine scanning mutagenesis; HIV-1; Six-helix bundle; gp41 Fusion core