Almost half of the eukaryotic proteome is inaccessible to standard experimental structure determination 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) 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. (2) 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, and (3) hnRNPA1, an RNA-binding protein able to undergo liquid-liquid phase separation in response to cellular stress.
I obtained my Ph.D. degree in 2012 from the University of Montpellier (France) under the supervision of Christian Roumestand and Catherine Royer. During my Ph.D. I used highpressure NMR spectroscopy to study the effects of hydrostatic pressure on protein folding and stability. I then joined the laboratory of Ad Bax at the NIH (Laboratory of Chemical Physics) as a postdoctoral fellow. In Ad Bax lab, I worked on a wide range of protein systems using solution NMR techniques, including amyloid peptides, disordered proteins and HIV-1 fusion protein gp41 and protease. I joined the Roy J. Carver Department of Biochemistry,
Biophysics and Molecular Biology at Iowa State University as an Assistant Professor in 2016. My research at ISU is focused on the structure and function of intrinsically disordered proteins and mixed folded proteins.
