119 269

Cited 121 times in

Bcl-x(L) sequesters its C-terminal membrane anchor in soluble, cytosolic homodimers.

Authors
Jeong, SY; Gaume, B; Lee, YJ; Hsu, YT; Ryu, SW; Yoon, SH; Youle, RJ
Citation
The EMBO journal, 23(10):2146-2155, 2004
Journal Title
The EMBO journal
ISSN
0261-41891460-2075
Abstract
Bcl-x(L) is a potent inhibitor of apoptosis. While Bcl-x(L) can be bound to mitochondria, a substantial fraction, depending on the cell type or tissue, is found in the cytosol of healthy cells. Gel filtration and crosslinking experiments reveal that, unlike monomeric Bax, Bcl-x(L) migrates in a complex of approximately 50 kDa in the cytosol. Co-immunoprecipitation experiments indicate that Bcl-x(L) in the cytosol forms homodimers. The C-terminal hydrophobic tails of two Bcl-x(L) molecules are involved in homodimer formation, and analysis of mutants demonstrates that the C-terminal lysine residue and the G138 residue lining the BH3-binding pocket are required for homodimerization. The flexible loop preceding the C-terminal tail in Bcl-x(L) is longer than that of several monomeric Bcl-2 family members and is a requisite for the homodimer formation. Bad binding to Bcl-x(L) dissociates the homodimers and triggers Bcl-x(L) binding to mitochondrial membranes. The C-terminal tail of Bcl-x(L) is also required to mediate Bcl-x(L)/Bax heterodimer formation. Both mitochondrial import and antiapoptotic activity of different Bcl-x(L) mutants correlate with their ability to form homodimers.
MeSH terms
Amino Acid SequenceAnimalsApoptosis/physiologyBinding SitesCarrier Proteins/metabolismCell LineCytoplasm/metabolismDimerizationHumansMitochondria/metabolismMolecular Sequence DataMutationPeptide Fragments/genetics/metabolismProtein Binding*Protein Structure, Quaternary*Protein Structure, SecondaryProto-Oncogene Proteins/genetics/metabolismProto-Oncogene Proteins c-bcl-2/*chemistry/genetics/metabolismSequence Alignmentbcl-2-Associated X Proteinbcl-Associated Death Proteinbcl-X Protein
DOI
10.1038/sj.emboj.7600225
PMID
15131699
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Neurosurgery
AJOU Authors
윤, 수한
Full Text Link
Files in This Item:
2146-2155.pdfDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse