title: Structural and Functional Study of Apoptosis-linked Gene-2·Heme-binding Protein 2 Interactions in HIV-1 Production.
abstract: In the HIV-1 replication cycle, the endosomal sorting complex required for transport (ESCRT) machinery promotes viral budding and release in the late stages. In this process, the ESCRT proteins, ALIX and TSG101, are recruited through interactions with HIV-1 Gag p6. ALG-2, also known as PDCD6, interacts with both ALIX and TSG101 and bridges ESCRT-III and ESCRT-I. In this study, we show that ALG-2 affects HIV-1 production negatively at both the exogenous and endogenous levels. Through a yeast two-hybrid screen, we identified HEBP2 as the binding partner of ALG-2, and we solved the crystal structure of the ALG-2·HEBP2 complex. The function of ALG-2·HEBP2 complex in HIV-1 replication was further explored. ALG-2 inhibits HIV-1 production by affecting Gag expression and distribution, and HEBP2 might aid this process by tethering ALG-2 in the cytoplasm.
authors: From the State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071.|the Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors: Jing
authors: J
authors: Ma
authors: the CAAS-Michigan State University Joint Laboratory of Innate Immunity, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, and.
authors: Xianfeng
authors: X
authors: Zhang
authors: From the State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071.
authors: Yanbin
authors: Y
authors: Feng
authors: From the State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071.
authors: Hui
authors: H
authors: Zhang
authors: the CAAS-Michigan State University Joint Laboratory of Innate Immunity, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, and.
authors: Xiaojun
authors: X
authors: Wang
authors: the CAAS-Michigan State University Joint Laboratory of Innate Immunity, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, and.
authors: Yonghui
authors: Y
authors: Zheng
authors: From the State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, wentaoqiao@nankai.edu.cn.|the Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors: Wentao
authors: W
authors: Qiao
authors: From the State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, liu2008@nankai.edu.cn.
authors: Xinqi
authors: X
authors: Liu
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003460:Crystallization; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D000081062:Heme-Binding Proteins; D006420:Hemeproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011257:Pregnancy Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D021381:Protein Transport; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*; D000099177:Tsg101 Protein
chemical_list: D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D011257:Pregnancy Proteins; D014157:Transcription Factors; D000099177:Tsg101 Protein; C516258:HEBP2 protein, human; C097753:PDCD6 protein, human; C117020:PDCD6IP protein, human
keywords: ALG-2; Gag expression; crystal structure; human immunodeficiency virus (HIV); inhibition mechanism; protein-protein interaction; transport; viral replication