title: Identification of the protein-protein contact site and interaction mode of human VDAC1 with Bcl-2 family proteins.
abstract: Bcl-2 family of proteins plays differential roles in regulation of mitochondria-mediated apoptosis, by either promoting or inhibiting the release of apoptogenic molecules from mitochondria to cytosol. Bcl-2 family proteins modulate the mitochondrial permeability through interaction with adenine nucleotide translocator (ANT), voltage-dependent anion channel (VDAC), ADP/ATP exchange, or oxidative phosphorylation during apoptosis. Although the mitochondrial homeostasis is affected by the relative ratio of pro- and anti-apoptotic Bcl-2 family members, the molecular mechanism underlying the release of mitochondrial intermembrane proteins remains elusive. Here we reported the biochemical evidence that both pro-apoptotic Bax and anti-apoptotic Bcl-X(L) might simultaneously contact the putative loop regions of human VDAC1, and the existence of VDAC1-Bax-Bcl-X(L) tertiary complex in vitro suggested that VDAC1 channel conformation and mitochondrial permeability could be determined by the delicate balance between Bax and Bcl-X(L).
authors.affiliation: The Center for Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Shi
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.forename: Changjiang
authors.initials: C
authors.lastname: Weng
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Zheng
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
mesh_terms: D001665:Binding Sites; D006801:Humans; D016297:Mutagenesis, Site-Directed; D018272:Porins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D050995:Voltage-Dependent Anion Channel 1; D050994:Voltage-Dependent Anion Channels; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: C494826:BAX protein, human; C494811:BCL2L1 protein, human; D018272:Porins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C494762:VDAC1 protein, human; D050994:Voltage-Dependent Anion Channels; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D050995:Voltage-Dependent Anion Channel 1