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Structural basis of BAM-mediated outer membrane β-barrel protein assembly

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机构: [1]State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China. [2]Department of Biophysics of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. [3]Center of Cryo Electron Microscopy, Zhejiang University, Hangzhou, China. [4]Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China. [5]Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. [6]Frontiers Medical Center, Tianfu Jincheng Laboratory, West China Hospital, Sichuan University, Chengdu, China. [7]Institute of Quantitative Biology, College of Life Sciences, Cancer Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. [8]Shanghai Institute for Advanced Study, Zhejiang University, Shanghai, China. [9]College of Life Science, Sichuan University, Chengdu, China. [10]School of Pharmaceutical Sciences, Wuhan University, Wuhan, China. [11]Department of Chemistry, Columbia University, New York, NY, USA.
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The outer membrane structure is common in Gram-negative bacteria, mitochondria and chloroplasts, and contains outer membrane β-barrel proteins (OMPs) that are essential interchange portals of materials1-3. All known OMPs share the antiparallel β-strand topology4, implicating a common evolutionary origin and conserved folding mechanism. Models have been proposed for bacterial β-barrel assembly machinery (BAM) to initiate OMP folding5,6; however, mechanisms by which BAM proceeds to complete OMP assembly remain unclear. Here we report intermediate structures of BAM assembling an OMP substrate, EspP, demonstrating sequential conformational dynamics of BAM during the late stages of OMP assembly, which is further supported by molecular dynamics simulations. Mutagenic in vitro and in vivo assembly assays reveal functional residues of BamA and EspP for barrel hybridization, closure and release. Our work provides novel insights into the common mechanism of OMP assembly.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.

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基金编号: 2018YFA0507700 2021YFA1301900 2021YFA1301203 2017YFA0504803 2021YFA1201201 2021YFF1200404 31900039 32170029 32000844 81971974 U1967217 BR-ZJU-SIAS-001 226-2022-00043 226-2022-00192 ZYYC20021 ZJZX2020014 SN-ZJU-SIAS-003/006/009 NCTIB2022HS02010 SYB202132

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大类 | 1 区 综合性期刊
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Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者机构: [1]State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.
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通讯机构: [1]State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China. [2]Department of Biophysics of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. [3]Center of Cryo Electron Microscopy, Zhejiang University, Hangzhou, China. [4]Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China. [5]Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. [7]Institute of Quantitative Biology, College of Life Sciences, Cancer Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. [8]Shanghai Institute for Advanced Study, Zhejiang University, Shanghai, China. [11]Department of Chemistry, Columbia University, New York, NY, USA.
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