Premium
Bcl‐2 is a monomeric protein: prevention of homodimerization by structural constraints
Author(s) -
Conus Sébastien,
Kaufmann Thomas,
Fellay Isabelle,
Otter Isabelle,
Rossé Thierry,
Borner Christoph
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.7.1534
Subject(s) - immunoprecipitation , biology , apoptosis , microbiology and biotechnology , biochemistry , gene
The pro‐apoptotic activity of the Bcl‐2 family member Bax has been shown to be facilitated by homodimerization. However, it is unknown whether Bcl‐2 or Bcl‐x L have to homodimerize to protect cells from apoptosis. Here we show by co‐immunoprecipitation and FPLC analyses that while Bax multimerizes and forms heterodimers with Bcl‐2, there is no evidence for Bcl‐2 homodimerization, even in conditions under which Bcl‐2 protects cells from apoptosis. Immunofluorescence studies confirmed that Bax can attract active, soluble Bcl‐2 to mitochondrial membranes, but that nuclear/ER membrane‐bound Bcl‐2 was incapable of dislocating soluble Bcl‐2. The failure of Bcl‐2 to homodimerize is due to structural constraints as versions of Bcl‐2 deleted or mutated in the BH1 and BH2 domains effectively dimerized with wild‐type Bcl‐2 and were dislocated by Bcl‐2 inside cells. These data indicate that naturally occurring Bcl‐2 does not expose protein domains that mediate homodimerization and therefore most likely acts as a monomer to protect cells from apoptosis.