16. Mechanism of Bcl-members Hengartner, Nature 407, 2000 GK '09 Pore formation Dimerization! (Not a mechanism!) Mediated interaction Ion channel Homeostasis Bcl2 family member
17.
Editor's Notes
GK 2009 a.a.m.thomas@uu.nl
GK 2009 a.a.m.thomas@uu.nl
GK 2009 a.a.m.thomas@uu.nl
GK 2009 a.a.m.thomas@uu.nl Formation of pore: Cyt c and other intermembrane proteins escape Heterodimerization between pro- and anti-apoptotic family members. Dimerization is achieved when the BH3 domain of one molecule binds into a hydrophobic pocket formed by the BH1, BH2 and BH3 domains of another family member72. Because of structural constraints, both homodimers and heterodimers are asymmetric molecules. Direct regulation of caspases via adaptor molecules, as has been described in C. elegans. Although the CED-4 homologue Apaf-1 is probably not a Bcl-2 family target, other adaptor proteins, such as BAR (ref. 73), the endoplasmic reticulum-localized protein Bap31 (ref. 74) and Aven (ref. 75), have been described in mammals. Interaction with other mitochondrial proteins, such as VDAC and the adenosine nucleotide transporter (ANT), either to generate a pore for cytochrome c exit, or to modulate mitochondrial homeostasis (for example, opening of the PTP). Oligomerization to form a weakly selective ion channeL