< Back to previous page

Project

An integrated molecular, functional and structural characterization of the determinants, underlying the multi-domain complexes between IP3 receptors and anti-apoptotic Bcl-2 and Bcl-Xl proteins

Intracellular Ca2+ signals play a critical role in multiple cellular processes, including proliferation and apoptosis. A key regulator of Ca2+–signaling is the inositol 1, 4, 5 trisphosphate (IP3) receptor (IP3R), which is the main intracellular Ca2+–release channel. The anti-apoptotic members of the B-cell lymphoma 2 (Bcl-2) family of proteins, Bcl-2 and Bcl-Xl, have emerged as distinct factors that critically control IP3R activity. Bcl-2 mainly acts as an IP3R inhibitor and Bcl-Xl as an IP3R sensitizer. In addition, IP3R regulation by these proteins appears to be complex, as it is affected by the level of agonist signaling and protein concentration. Yet, the underlying mechanisms of these divergent functional interactions between IP3Rs and Bcl–2 on the one hand and IP3Rs and Bcl–Xl on the other hand remain poorly understood at the molecular level. We therefore aim to elucidate the molecular determinants underlying IP3R/Bcl-2- and IP3R/Bcl-Xl-complex formation by using an integrated set of state-of-the-art biochemical, biophysical, cell biological and structural approaches.

Date:1 Oct 2017 →  1 Nov 2019
Keywords:IP3 receptors, Bcl-2, Bcl-Xl proteins
Disciplines:Medicinal and biomolecular chemistry, Molecular and cell biology, Plant biology, Systems biology, Biophysics