BH3 binding specificity ‘in vivo’
The affinities of BH3-only proteins for their pro-survival targets varies greatly: Whereas Bim and Puma bind all five pro-survival Bcl-2 family members with high (low nM) affinity, Bad binds only Bcl-2, Bcl-xL and Bcl-w, whereas Noxa binds only Mcl-1 and A1. Since the binding specificity of BH3-only proteins greatly affects their ability to kill cells, we are modifying the mouse Bim gene in situ by replacing its BH3 domain with that of Bad, Noxa or Puma, to determine how changing its binding specificity affects the biological activity of Bim in vivo