Bak apoptotic pores involve a flexible C-terminal region and juxtaposition of the C-terminal transmembrane domains

Cell Death and Differentiation
S IyerRuth M Kluck

Abstract

Bak and Bax mediate apoptotic cell death by oligomerizing and forming a pore in the mitochondrial outer membrane. Both proteins anchor to the outer membrane via a C-terminal transmembrane domain, although its topology within the apoptotic pore is not known. Cysteine-scanning mutagenesis and hydrophilic labeling confirmed that in healthy mitochondria the Bak α9 segment traverses the outer membrane, with 11 central residues shielded from labeling. After pore formation those residues remained shielded, indicating that α9 does not line a pore. Bak (and Bax) activation allowed linkage of α9 to neighboring α9 segments, identifying an α9:α9 interface in Bak (and Bax) oligomers. Although the linkage pattern along α9 indicated a preferred packing surface, there was no evidence of a dimerization motif. Rather, the interface was invoked in part by Bak conformation change and in part by BH3:groove dimerization. The α9:α9 interaction may constitute a secondary interface in Bak oligomers, as it could link BH3:groove dimers to high-order oligomers. Moreover, as high-order oligomers were generated when α9:α9 linkage in the membrane was combined with α6:α6 linkage on the membrane surface, the α6-α9 region in oligomerized Bak is flexible. These ...Continue Reading

References

May 23, 1997·The Journal of Biological Chemistry·Y T Hsu, R J Youle
Jan 7, 1998·The Journal of Cell Biology·K G WolterR J Youle
Oct 8, 1998·The Journal of Cell Biology·I S GopingG C Shore
Jan 8, 2000·The Journal of Biological Chemistry·A GründlingR Young
Mar 10, 2001·Journal of Molecular Biology·R P RiekR M Graham
Dec 26, 2001·Biophysical Journal·María del Mar Martínez-SenacJuan C Gómez-Fernández
Jan 8, 2003·The Journal of Cell Biology·Thomas KaufmannChristoph Borner
Jul 26, 2003·Science·Emily H Y ChengStanley J Korsmeyer
Nov 19, 2003·Journal of Molecular Biology·Motoshi SuzukiNico Tjandra
Mar 24, 2004·The Journal of Cell Biology·Anna SchinzelChristoph Borner
Mar 31, 2004·Journal of Molecular Biology·Jichun MaTomitake Tsukihara
May 28, 2005·The EMBO Journal·Matthew G AnnisDavid W Andrews
Dec 13, 2006·Molecular Cell·Tudor MoldoveanuKalle Gehring
Oct 2, 2007·Biochimica Et Biophysica Acta·Alejandro TorrecillasJuan C Gómez-Fernández
May 9, 2008·Nucleic Acids Research·Christian ColeGeoffrey J Barton
Oct 25, 2008·Nature·Evripidis GavathiotisLoren D Walensky
Nov 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jamie I FletcherJerry M Adams
May 7, 2009·Biochemistry·Endah S Sulistijo, Kevin R Mackenzie
Dec 17, 2009·The Journal of Biological Chemistry·Stephanie BleickenEnrica Bordignon
Aug 5, 2010·Nature Reviews. Molecular Cell Biology·Stephen W G Tait, Douglas R Green
Sep 21, 2010·The Journal of Biological Chemistry·Michael LazarouMichael T Ryan
Nov 3, 2010·The Journal of Biological Chemistry·Han DuTomomi Kuwana
Jan 5, 2011·Biochimica Et Biophysica Acta·Dana WestphalRuth M Kluck
Jan 20, 2011·Journal of Cell Science·Juan Garcia ValeroAbdel Aouacheria
Oct 22, 2011·Cell Death and Differentiation·G DewsonR M Kluck
Nov 29, 2011·Biochimica Et Biophysica Acta·Marco Colombini, Carmen A Mannella
May 18, 2012·Molecular Pharmaceutics·Rebecca J BoohakerAnnette R Khaled

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Citations

Dec 15, 2015·The FEBS Journal·Mark P A Luna-Vargas, Jerry E Chipuk
Jul 7, 2016·Scientific Reports·Chenyi LiaoJianing Li
Mar 23, 2017·Biochimica Et Biophysica Acta. Biomembranes·Lilit SimonyanStéphen Manon
Oct 7, 2017·Viruses·Marc KvansakulMark G Hinds
Nov 4, 2017·Cell Death and Differentiation·Jerry M Adams, Suzanne Cory
Dec 13, 2017·Cell Death and Differentiation·Lisa M LindqvistDavid L Vaux
Jun 21, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Rachel T UrenRuth M Kluck
Dec 24, 2018·The EMBO Journal·Jonathan P BernardiniGrant Dewson
Oct 2, 2019·Cells·Hector Flores-Romero, Ana J García-Sáez
Oct 2, 2019·Cold Spring Harbor Perspectives in Biology·Tudor Moldoveanu, Peter E Czabotar
Dec 29, 2016·Proceedings of the National Academy of Sciences of the United States of America·Vicente Andreu-FernándezMar Orzáez
Jan 13, 2018·Apoptosis : an International Journal on Programmed Cell Death·Ali RazaghiSpencer B Gibson
Jul 5, 2017·Proceedings of the National Academy of Sciences of the United States of America·Mark Xiang LiGrant Dewson
Oct 9, 2019·Nature Chemical Biology·Mark F van DelftBenjamin T Kile
Sep 16, 2020·Nature Structural & Molecular Biology·Angus D CowanPeter E Czabotar
Jun 3, 2017·Scientific Reports·Mingzhen ZhangBuyong Ma
Sep 7, 2018·Cell Death and Differentiation·Stephanie BleickenEnrica Bordignon
Jan 1, 2018·Cell Death and Differentiation·Jerry M Adams, Suzanne Cory
Apr 2, 2021·Molecular Cell·Richard W BirkinshawPeter E Czabotar
Sep 16, 2021·The EMBO Journal·Jarrod J SandowGrant Dewson

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis