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Conformational Dynamics of basic leucine zipper regions of ATF4

Aug 17, 2022 - 10:00 AM
to Aug 17, 2022 - 12:00 PM

The next Bioscience Work-in-Progress (Bio-WIP) Seminar will be presented by Urval Patel, a graduate student from the Julien Roche Lab in the Roy J. Carver Department of Biochemistry, Biophysics & Molecular Biology.

Abstract: Almost half of the eukaryotic proteome belongs to the so-called “dark proteome” which is constituted for a large part of intrinsically disordered proteins and proteins containing at least one long disordered domain. The goal of this project is to characterize the structural and dynamical properties of one of such proteins, containing both disordered and structured regions: the transcription factor ATF4. ATF4 plays a key role in mediating cellular gene expression changes in response to different types of cellular stresses, including endoplasmic reticulum stress, amino acid deprivation, and oxidative stress. ATF4 is composed of two functional domains: an N-terminal transactivation domain (TAD) and a C-terminal basic-leucine zipper domain (bZip). The C-terminal bZip domain encompasses a basic region essential for DNA binding and leucine zipper region essential for homo/heterodimerization. We use here a combination of molecular dynamics simulations and solution NMR spectroscopy to investigate the conformational dynamics of the isolated bZip domain of ATF4. Our results suggest that in the absence of DNA the leucine zipper region forms a highly ordered a-helix, while the basic region populates an ensemble of predominantly disordered and highly dynamic conformations.  

The Bio-WIP Seminars (formerly BBMB WIP seminars) are sponsored by the BBMB Graduate Learning Community. All are welcome to join!