Séminaire de Saron Catak : "Impact of Deamidation on Bcl-xL Structure and Function: A Molecular Dynamics Perspective"

Le Pr Saron Catak, Department of Chemistry, Bogazici University, Bebek, Istanbul, Turkiye, professeure invitée de l'université de Bordeaux pour 10 mois, donnera un séminaire à l'IBGC le 7 mars à 11h, axé sur de la modélisation moléculaire, qui ouvrira sur un workshop de dynamique moléculaire pour les volontaires (inscriptions auprès de Muriel Priault).

07 Mars 2024

Salle de conférence de l'IBGC, Campus Carreire,

Impact of Deamidation on Bcl-x_L Structure and Function: A Molecular Dynamics Perspective

Deamidation is a non-enzymatic biochemical reaction that occurs spontaneously in peptides and proteins.¹ Many reports show that changes accompanying deamidation have a substantial effect on protein structure, which dramatically affect protein function and stability.² Deamidation is also believed to play a large role in the development of tumors.³ This project aims to explore the relationship between deamidation and disease by means of computational techniques. The protein of particular interest, Bcl-xL, is the dominant inhibitor of apoptosis. Notably, Bcl-xL undergoes post-translational modifications (PTMs) on its loop region (intrinsically disordered region-IDR), which is also the essential site for deamidation. Deamidation on the IDR of Bcl-xL induces loss of anti-apoptotic function, hence, is a pivotal switch that regulates its biological function. This transmembrane protein found in the mitochondria, plays a critical role in cancer development and resistance to treatment.³ Consequently, this mechanism could be one of the keys to unraveling –at the molecular level– the critical role Bcl-xL plays in cancer therapy resistance.⁴

Deamidation-induced conformational changes in Bcl-xL were explored to gain insight into its loss of function by performing molecular dynamics simulations.⁵ The outcomes of this study will provide a unique perspective on the underlying mechanism of Bcl-xL deamidation-induced cell death. Understanding the dynamics of the IDR and the structural changes upon its deamidation plays a crucial role in elucidating potential impacts of deamidation on the structure and function of Bcl-xL. This study aimed to computationally unravel the structural consequences of deamidation that lead to loss of Bcl-xL anti-apoptotic function at the atomic level. The outcomes of this project are expected to pave the way for future experimental and computational studies.

References:

1 Robinson, N. E., Robinson, A. B. Proc. Natl. Acad. Sci. USA 2001, 98, 944.

2 Weintraub, S.J. Deverman, B.E. Sci. STKE. 2007, 409, re7.

3 Takehara, T., Takahashi, H. Cancer Research 2003, 63, 3054.

4 Priault, M. Biochim. Biophys. Acta - Mol. Cell Res. 2017, 1864, 1734.

5 Catak, S. J. Chem. Inf. Model. 2022, 62, 1, 102.

IBGC is fortunate to host Pr Saron Catak (University of Bogazici, Istanbul) as a Visiting Scholar until the end of July. Saron is a computational chemist and an expert in molecular modeling. As part of her visiting appointment, she offers to give a talk at IBGC on March 7th at 11 AM to help us discover or improve our knowledge on molecular dynamics.

Saron also offers to provide a hands-on training workshop for anyone (from M1 students to emeritus scientists) interested in retrieving a protein structure from the RSCB protein databank and learn all the steps to prep the system for molecular simulations using Amber. Saron will then provide the results of a molecular dynamics simulation to show how to interpret and post-process the simulation data. This workshop will be held on March 14th from 2 PM to 5 PM. More details on the organization will follow.

Because the number of computers is limited, ideally only 12 people can register for this training. But if more would like to be trained, Saron is willing to organize another workshop in April.

Please contact muriel.priault@ibgc.cnrs.fr to sign up for the workshop.