Friday Oct 28 at 11 AM

A. Keith Dunker, Ph.D.
Professor of Biochemistry and Molecular Biology Professor of Informatics Director,
 Center for Computational Biology and Bioinformatics Department of Biochemistry 
and Molecular Biology Indiana University School of Medicine

Intrinsic Disorder and Functional Proteomics

Many proteins contain regions that lack specific 3-D structure; indeed some proteins 
lack specific 3-D structure in their entireties under physiological conditions and 
yet carry out function as indicated by appropriate biochemical assays.  Such proteins 
and regions have been called natively unfolded, intrinsically unstructured, naturally
 disordered, and rheomorphic, and various combinations of these terms among others. 
Such intrinsically disordered proteins and regions can exist as extended, random-coil-like
 ensembles, as compact, molten-globule-like ensembles, or as interconverting forms
 occupying either structural ensemble at different times. Sites of protein phosphorylation,
 the proline-rich motif that associates with SH3 domains, PEST sequences, sites 
of ubiquitination, and sites associated with calmodulin binding are all indicated 
to be located preferentially in regions of intrinsic disorder.  Additional evidence 
suggests intrinsic disorder is involved in many of the well characterized signaling 
interactions.  Regions of pre-mRNA that are differentially excised in alternative 
splicing appear to code for segments of intrinsic disorder much more often than 
for segments of structured protein.  Taken together these data suggest that 
understanding and characterizing intrinsically disordered proteins will be important 
for functional proteomics.