title: Solution Structure of Apoptotic BAX Oligomer: Oligomerization Likely Precedes Membrane Insertion.
abstract: Proapoptotic BAX protein is largely cytosolic in healthy cells, but it oligomerizes and translocates to mitochondria upon receiving apoptotic stimuli. A long-standing challenge has been the inability to capture any structural information beyond the onset of activation. Here, we present solution structures of an activated BAX oligomer by means of spectroscopic and scattering methods, providing details about the monomer-monomer interfaces in the oligomer and how the oligomer is assembled from homodimers. We show that this soluble oligomer undergoes a direct conversion into membrane-inserted oligomer, which has the ability of inducing apoptosis and structurally resembles a membrane-embedded oligomer formed from BAX monomers in lipid environment. Structural differences between the soluble and the membrane-inserted oligomers are manifested in the C-terminal helices. Our data suggest an alternative pathway of apoptosis in which BAX oligomer formation occurs prior to membrane insertion.
authors: Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors: Tai-Ching
authors: TC
authors: Sung
authors: Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors: Ching-Yu
authors: CY
authors: Li
authors: Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors: Yei-Chen
authors: YC
authors: Lai
authors: Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors: Chien-Lun
authors: CL
authors: Hung
authors: National Synchrotron Radiation Research Center, Hsinchu 30076, Taiwan.
authors: Orion
authors: O
authors: Shih
authors: National Synchrotron Radiation Research Center, Hsinchu 30076, Taiwan.
authors: Yi-Qi
authors: YQ
authors: Yeh
authors: National Synchrotron Radiation Research Center, Hsinchu 30076, Taiwan.
authors: U-Ser
authors: US
authors: Jeng
authors: Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan. Electronic address: ywchiang@mx.nthu.edu.tw.
authors: Yun-Wei
authors: YW
authors: Chiang
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics*; D001665:Binding Sites; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008928:Mitochondria / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein
keywords: Apoptosis; Double electron-electron resonance; Spin-label electron spin resonance