Intrinsically Disordered Proteins

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CIS Colloquium, Feb 04, 2013, 11:00AM – 12:00PM, Tech Center 111

Intrinsically Disordered Proteins

A. Keith Dunker , Indiana University School of Medicine

The standard view is that each protein’s amino acid sequence provides the information for it to fold into a specific 3D structure, and the active site formed within this structure carries out function. Indeed, current biology and biochemical textbooks suggest that virtually all proteins act via this sequence-to-structure-to-function paradigm. These views are correct for enzymes, which function as catalysts that accelerate chemical reactions. But a cell is not just an unregulated bag of enzyme-catalyzed chemical reactions. Biological processes, such as cell division, development of different cell types, etc. require a coordinated regulation and organization of the various cellular components and compartments as well as regulation of the various chemical reactions. These regulatory functions involve proteins that interact with each other and with nucleic acids via complex networks. We have used computational and bioinformatics methods to show that the regulatory signaling interactions in cells depend not only on protein 3D structure, but also depend on intrinsically disordered proteins and intrinsically disordered protein regions. This lecture will cover four topics: 1. Order / disorder for ~ 3,500 proteomes; 2. Improving protein solubility with intrinsically disordered tails; 3. Intrinsically disordered proteins and stochastic machines; and, if time permits, 4. The importance of intrinsic disorder in the evolution of very early proteins.

A. Keith Dunker received a broad education, with degrees in chemistry (UC Berkeley, 1965), physics (UW Madison, 1967), and biophysics (UW Madison, 1969), and with postdoctoral training in structural biology (1969-1973, Yale University). After spending a career using biophysics and spectroscopy to study virus and phage structure and assembly especially for the purposes of understanding structures and functions of viral capsid proteins, in the middle 1980s Dr. Dunker realized the coming importance of computational biology and bioinformatics and began to teach, to work and especially to collaborate “on the side” in these newly developing areas. His biophysics work and his computational hobby merged in the mid-1990s with the realization that many proteins lacked 3D structure yet carried out function and could be studied as a group using bioinformatics approaches and methods. His “second career,” which focuses on the bioinformatics of intrinsically disordered proteins, is leading to novel ideas regarding protein structure and function, and these will be the topics of his seminar. More recently he has gone “back-to-the-bench” to carry out biophysics experiments to test ideas and hypotheses for the functions and activities of intrinsically disordered proteins developed in the bioinformatics work.