Intrinsically Disordered Proteins and Multi-cellular Organisms

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CIS Colloquium, Dec 17, 2014, 11:00AM – 12:00PM, SERC 306

Intrinsically Disordered Proteins and Multi-cellular Organisms

A. Keith Dunker , Department of Biochemistry & Molecular Biology Indiana University Schools of Medicine & Informatics

Intrinsically disordered proteins (IDPs) and IDP regions lack stable tertiary structure yet carry out numerous biological functions, especially those associated with signaling, transcription regulation, DNA condensation, cell division, and cellular differentiation. Both post-translational modifications (PTMs) and alternative splicing (AS) expand the functional repertoire of IDPs. Here we propose that an “IDP-based developmental toolkit,” which is comprised of IDP regions, PTMs, especially multiple PTMs, within these IDP regions, and AS events within segments of pre-mRNA that code for these same IDP regions, enabled sufficient functional diversification and signaling responsiveness so that natural selection could lead to the evolution of complex multicellular organisms.

A. Keith Dunker received a broad education in chemistry (B.S., UC Berkeley), physics and biophysics (M.S. and Ph.D., UW Madison), and structural biology (Postdoctoral Work, Yale University), followed by a 30-year research focus on the structure, assembly, and molecular biology of viruses and phages. In a study of a model system for membrane penetration by fd phage, conversion from rigid structure to molten-globular disorder enabled the fd capsid protein to insert into lipid bilayers and thereby transport the phage DNA across the membrane. Simply put, the phage capsid lost structure and thereby gained function. After an incubation period of several years during which time several additional examples were noticed of function arising from absence or loss of protein structure, the particular example of calcineurin’s disorder-based regulation was presented in a seminar by Chuck Kissinger. This work stimulated Dr. Dunker to switch, with the aid of Zoran Obradovic, to computational studies on intrinsically disordered proteins on November 15, 1995 at 12:40 PM (see T. Chouard, Breaking the Protein Rules, Nature, 2011, 471, 151-153).