Interaction of a putative BH3 domain of clusterin with anti-apoptotic Bcl-2 family proteins as revealed by NMR spectroscopy

► Identification of a conserved BH3 motif in C-terminal coiled coil region of nCLU. ► The nCLU BH3 domain binds to BH3 peptide-binding grooves in both Bcl-XL and Bcl-2. ► A conserved binding mechanism of nCLU BH3 and the other pro-apoptotic BH3 peptides with Bcl-XL. ► The absolutely conserved Leu323 and Asp328 of nCLU BH3 domain are critical for binding to Bcl-XL. ► Molecular understanding of the pro-apoptotic function of nCLU as a novel BH3-only protein.