title: Bax forms an oligomer via separate, yet interdependent, surfaces.
abstract: Interactions of Bcl-2 family proteins regulate permeability of the mitochondrial outer membrane and apoptosis. In particular, Bax forms an oligomer that permeabilizes the membrane. To map the interface of the Bax oligomer we used Triton X-100 as a membrane surrogate and performed site-specific photocross-linking. Bax-specific adducts were formed through photo-reactive probes at multiple sites that can be grouped into two surfaces. The first surface overlaps with the BH1-3 groove formed by Bcl-2 Homology motif 1, 2, and 3; the second surface is a rear pocket located on the opposite side of the protein from the BH1-3 groove. Further cross-linking experiments using Bax BH3 peptides and mutants demonstrated that the two surfaces interact with their counterparts in neighboring proteins to form two separated interfaces and that interaction at the BH1-3 groove primes the rear pocket for further interaction. Therefore, Bax oligomerization proceeds through a series of interactions that occur at separate, yet allosterically, coupled interfaces.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73126, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Weijia
authors.initials: W
authors.lastname: Zhu
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Lapolla
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Miao
authors.forename: Yuanlong
authors.initials: Y
authors.lastname: Shao
authors.forename: Mina
authors.initials: M
authors.lastname: Falcone
authors.forename: Doug
authors.initials: D
authors.lastname: Boreham
authors.forename: Nicole
authors.initials: N
authors.lastname: McFarlane
authors.forename: Jingzhen
authors.initials: J
authors.lastname: Ding
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Johnson
authors.forename: Xuejun C
authors.initials: XC
authors.lastname: Zhang
authors.forename: David W
authors.initials: DW
authors.lastname: Andrews
authors.forename: Jialing
authors.initials: J
authors.lastname: Lin
mesh_terms: D000495:Allosteric Site; D020816:Amino Acid Motifs; D017209:Apoptosis; D001671:Biochemistry / Q000379:methods; D003432:Cross-Linking Reagents / Q000737:chemistry; D003902:Detergents / Q000494:pharmacology; D006801:Humans; D009154:Mutation; D017830:Octoxynol / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; D003902:Detergents; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D017830:Octoxynol
references.citation: Genes Dev. 2005 Jun 1;19(11):1294-305
references.pmid: 15901672
references.citation: J Biol Chem. 1998 Apr 24;273(17):10777-83
references.pmid: 9553144
references.citation: Science. 1997 Feb 14;275(5302):983-6
references.pmid: 9020082
references.citation: Mol Cell Biol. 2000 Feb;20(3):929-35
references.pmid: 10629050
references.citation: Cell Death Differ. 2008 Oct;15(10):1564-71
references.pmid: 18551131
references.citation: J Biol Chem. 2003 Jul 4;278(27):25039-45
references.pmid: 12721291
references.citation: J Biol Chem. 2004 Oct 15;279(42):43920-8
references.pmid: 15302859
references.citation: J Cell Biol. 1999 Mar 8;144(5):891-901
references.pmid: 10085289
references.citation: J Biol Chem. 1997 May 23;272(21):13829-34
references.pmid: 9153240
references.citation: J Cell Biol. 2004 Mar 29;164(7):1021-32
references.pmid: 15037603
references.citation: Mol Cell. 2009 Nov 13;36(3):487-99
references.pmid: 19917256
references.citation: J Biol Chem. 1996 Mar 29;271(13):7440-4
references.pmid: 8631771
references.citation: PLoS Biol. 2008 Jun 10;6(6):e147
references.pmid: 18547146
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20327-32
references.pmid: 19074266
references.citation: Immunity. 2003 Sep;19(3):341-52
references.pmid: 14499110
references.citation: J Biol Chem. 2001 Apr 13;276(15):11615-23
references.pmid: 11136736
references.citation: EMBO J. 2005 Jun 15;24(12):2096-103
references.pmid: 15920484
references.citation: Cancer Cell. 2002 Sep;2(3):183-92
references.pmid: 12242151
references.citation: Science. 2001 Apr 27;292(5517):727-30
references.pmid: 11326099
references.citation: J Biol Chem. 2003 Dec 5;278(49):48935-41
references.pmid: 14522999
references.citation: J Biol Chem. 2001 Nov 9;276(45):41733-41
references.pmid: 11535589
references.citation: Mol Cell. 2009 Nov 25;36(4):696-703
references.pmid: 19941828
references.citation: Cell. 2008 Dec 12;135(6):1074-84
references.pmid: 19062087
references.citation: Mol Cell. 2004 Dec 3;16(5):807-18
references.pmid: 15574335
references.citation: Nature. 2008 Oct 23;455(7216):1076-81
references.pmid: 18948948
references.citation: Gene. 1989 Apr 15;77(1):51-9
references.pmid: 2744487
references.citation: J Biol Chem. 2005 Mar 18;280(11):10587-98
references.pmid: 15590655
references.citation: Science. 2007 Feb 9;315(5813):856-9
references.pmid: 17289999
references.citation: EMBO J. 2006 Jun 7;25(11):2287-96
references.pmid: 16642033
references.citation: Nat Cell Biol. 2006 Dec;8(12):1348-58
references.pmid: 17115033
references.citation: Nat Rev Mol Cell Biol. 2008 Jan;9(1):47-59
references.pmid: 18097445
references.citation: J Biol Chem. 2006 May 26;281(21):14764-75
references.pmid: 16571718
references.citation: Nature. 1994 May 26;369(6478):321-3
references.pmid: 8183370
references.citation: Biochem J. 2000 Jan 15;345 Pt 2:271-8
references.pmid: 10620504
references.citation: Genes Dev. 2000 Aug 15;14(16):2060-71
references.pmid: 10950869
references.citation: Mol Cell. 2008 May 9;30(3):369-80
references.pmid: 18471982
references.citation: Apoptosis. 2007 May;12(5):897-911
references.pmid: 17453159
references.citation: J Biol Chem. 2009 Sep 4;284(36):23935-46
references.pmid: 19564333
references.citation: Mol Cell Biol. 1998 Oct;18(10):6083-9
references.pmid: 9742125
references.citation: EMBO J. 2001 Nov 15;20(22):6306-15
references.pmid: 11707402
references.citation: Science. 2003 Jul 25;301(5632):513-7
references.pmid: 12881569
references.citation: Apoptosis. 2007 May;12(5):887-96
references.pmid: 17453158
references.citation: Cell Death Differ. 2007 Mar;14(3):447-52
references.pmid: 16946732
references.citation: Cell. 1993 Aug 27;74(4):609-19
references.pmid: 8358790
references.citation: Cell. 2000 Nov 10;103(4):645-54
references.pmid: 11106734
references.citation: EMBO J. 1999 May 4;18(9):2330-41
references.pmid: 10228148
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):17975-80
references.pmid: 16330765
references.citation: Methods Enzymol. 1990;182:277-82
references.pmid: 2314241
references.citation: J Cell Biol. 1997 Dec 1;139(5):1281-92
references.pmid: 9382873
references.citation: J Cell Biol. 2009 Aug 10;186(3):355-62
references.pmid: 19651893
references.citation: J Cell Sci. 2009 Aug 15;122(Pt 16):2801-8
references.pmid: 19795525
references.citation: Proc Natl Acad Sci U S A. 1986 Nov;83(22):8604-8
references.pmid: 3095839
references.citation: Mol Cell. 2006 Dec 8;24(5):677-688
references.pmid: 17157251