Sequence | Protein | Binding to mitochondria | Cytochrome c release | ||
---|---|---|---|---|---|
Yeast | Mammals | Yeast | Mammals | ||
(1) Role of ART and Proline residues at positions 8 and 13 | |||||
-P8RGGGP13- | full length Bax | +/− | +/− | +/− | +/− |
BaxΨ/ΔART | +++ | +++ | +++ | +++ | |
-G8RGGGG13- | ART mutant | +++ | n.d. | +++ | n.d. |
-V8RGGGV13- | ART mutant | n.d. | +++ | n.d. | +++ |
-V8RGGGP13- | ART mutant | n.d. | +/− | n.d. | +/− |
-P8RGGGV13- | ART mutant | n.d. | +++ | n.d. | +++ |
(2) Role of helix α1 | |||||
-A24LLL27- | BaxΨ/ΔART | +++ | +++ | +++ | +++ |
BaxΨ/ΔARTΔHα1 | n.d. | − | n.d. | − | |
-R24LLL27- | BaxΨ/ΔARTHα1 mutant | + | − | + | − |
-A24LGV27- | BaxΨ/ΔARTHα1 mutant | +++ | − | +++ | − |
(3) Interaction between ART and BH2 (helix α7/8) | |||||
-P8RGGGP13--I152QDQG156- | full length human Bax | +/− | +/− | +/− | +/− |
-P8EGGGP13--I152QDQG156- | ART mutant | +++ | n.d. | +++ | n.d. |
-P8RGGGP13--I152QKQG156- | BH2 mutant | +++ | n.d. | +++ | n.d. |
-P8EGGGP13--I152QKQG156- | ART mutantBH2 mutant | − | n.d. | − | n.d. |
(1) The substitution of prolines 8 and 13, like the complete deletion of the 20 N-terminal residues, increase Bax binding and activity both in yeast and mammals; (2) substitutions in helix α1 decrease the binding of BaxΨ in mammals. The decrease is partly visible in yeast; (3) individual point mutations inverting charges in ART and in BH2 induce stimulation of Bax in yeast, but a double charge change revert to the wild-type behavior of Bax, suggesting the existence of an interaction between charged residues in these two domains, stabilizing the inactive conformation. Bold residues indicate mutations. −: inactive; n.d.: not determined; +/−: poorly active; +: active; +++: strongly active
The work done in the lab of the author has been supported by the CNRS, the Université de Bordeaux, and the Ligue Régionale contre le Cancer. The author thanks all his present and former students and colleagues for these studies, namely Nadine Camougrand, Muriel Priault, Hubert Arokium, Ingrid Bhatia-Kiššová, Thibaud Renault, Dario Trindade, Lilit Simonyan and Akandé Rouchidane Eyitayo.
The author contributed solely to the work.
The author declares no conflict of interest.
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© The Author(s) 2022.