"How disordered is disorder? An atomistic level view of mixed folded proteins"

Wed, Apr 21, 2021 - 12:00 PM — Wed, Apr 21, 2021 - 01:00 PM
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Julien F. Roche, Assistant Professor, Department of Biochemistry, Biophysics & Molecular Biology, Iowa State University, will give a seminar on "How disordered is disorder? An atomistic level view of mixed folded proteins."


Almost half of the eukaryotic proteome is inaccessible to standard experimental structure determination techniques and homology modeling. The largest fraction of this “dark proteome” is constituted of intrinsically disordered proteins and proteins containing at least one long disordered domain. We will focus here on the latter case: proteins containing both disordered and structured regions, also called “mixed folded proteins”. We  will review the range of biophysical techniques available for the characterization of mixed folded proteins and illustrate the important biological functions of these proteins with three examples: (1) hnRNPA1, an RNA-binding protein able to undergo liquid-liquid phase separation in response to cellular stress, (2) DISC1, a long scaffold protein that plays a pivotal role in regulating divergent signaling pathways in neurons, including cAMP/PKA, Akt/mTor, and GSK3b/b-catenin, and (3) ATF4, a key transcription factor mediating cellular gene expression changes in response to different types of cellular stresses, including endoplasmic reticulum stress, amino acid deprivation, and oxidative stress.

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