Journal of Proteomics & Bioinformatics
Open Access

Ligand binding and membrane insertion compete with oligomerization of the BclXL apoptotic repressor

2^nd International Conference on Proteomics & Bioinformatics

July 2-4, 2012 Embassy Suites Las Vegas, USA

Amjad farooq

Accepted Abstracts: J Proteomics Bioinform

Abstract :

BclXL apoptotic repressor plays a central role in determining the fate of cells to live or die during physiological processes such as embryonic development and tissue homeostasis. Herein, using a myriad of biophysical and bioinformatics techniques, we provide evidence that ligand binding and membrane insertion compete with oligomerization of BclXL in solution. Of particular importance is the observation that such oligomerization is driven by the intermolecular binding of its C-terminal transmembrane (TM) domain to the canonical hydrophobic groove in a domain-swapped trans-fashion, whereby the TM domain of one monomer occupies the canonical hydrophobic groove within the other monomer and vice versa. Binding of BH3 ligands to the canonical hydrophobic groove displaces the TM domain in a competitive manner allowing BclXL to dissociate into monomers upon heteroassociation. Remarkably, spontaneous insertion of BclXL into DMPC/DHPC bicelles results in a dramatic conformational change such that it can no longer recognize the BH3 ligands in what has come to be known as the ?hit-and-run? mechanism. Collectively, our data suggest that oligomerization of a key apoptotic repressor serves as an allosteric switch that fine tunes its ligand binding and membrane insertion pertinent to the regulation of apoptotic machinery.

Biography :

Amjad Farooq?s scientific interests include the application of a diverse array of biophysical techniques to decipher macromolecular interactions at hydrodynamic, thermodynamic, kinetic and structural level in the context of key signaling circuitry pertinent to cell growth and differentiation, cell cycle regulation, apoptosis and cancer. With more than 50 publications of wide international acclaim, Prof Farooq remains deeply devoted to the advancement of scientific and biomedical knowledge to help pave the way for the development of novel therapies harboring greater efficacy coupled with less toxicity for the treatment of disease. Importantly, he serves on the reviewing boards of various scientific journals and is heavily involved in grant study sections, including NIH and DOD.