Structural Analysis of the Interaction between Bcl-xL and the Noncanonical BH3 Domain of Non-Bcl-2 Family Proteins

Anti-apoptotic and anti-autophagic Bcl-2 homologues commonly contain a hydrophobic groove in which the BH3 domain is accommodated. The BH3 domain is usually considered a feature of Bcl-2 family members; however, it has also been found in various non-Bcl-2 family proteins. Although interactions among Bcl-2 family members have been extensively investigated and highlighted, those mediated by the BH3 domain of non-Bcl-2 family proteins have not been the focus of substantial research. In this review, the author conducted a structural analysis of Bcl-xL complexed with the BH3 domain of four non-Bcl-2 family proteins, Beclin 1, SOUL, TCTP, and Pxt1, at an atomic level. Although the overall Bcl-xL-binding modes are similar among these proteins, they are characterized by limited sequence conservation of the BH3 consensus motif and differences in residues involved in complex formation. Based on the structural analysis, the author suggests that more undiscovered BH3 domain-containing proteins might exist, which have been unidentified due to their limited sequence conservation but can bind to Bcl-2 family proteins and control apoptosis, autophagy, or other biological processes.

Automated summary

Anti-apoptotic and anti-autophagic Bcl-2 homologues commonly have a hydrophobic groove that accommodates the BH3 domain. Although the BH3 domain is typically associated with Bcl-2 family members, it has also been found in various non-Bcl-2 family proteins. The author conducted a structural analysis of Bcl-xL complexed with the BH3 domains of four non-Bcl-2 family proteins and suggests that there may be more undiscovered BH3 domain-containing proteins that can control apoptosis, autophagy, or other biological processes.