Mini-symposium on Protein design, structure determination and intrinsic structural disorder
The Department of Biology and the REPIN, BRAINSTRUC and PRISM centres are pleased to invite you to a mini-symposium on a range of current and important topics in protein science. No registration is required, and the symposium is open to all.
Programme
13:00-13:45
Ingemar André, Lund University Computational design of protein and peptide self-assembly
13:55-14:40
Frank DiMaio, University of Washington, Improving protein structure determination through data-driven forcefield optimization
15:00-16:00
A. Keith Dunker, Indiana University School of Medicine Intrinsically Disordered Proteins, Alternative Splicing, and Post-translational Modification (IDP-AS-PTM): A Toolkit for Developmental Biology
About the speakers
Ingemar André, Department of Biochemistry and Structural Biology, Lund University
Prof. André’s research lies at the interface between computational and experimental protein science, and deals with, for example, designing protein assemblies, using computational structural biology to study evolution and developing and applying methods to study conformational ensembles in solution.
Publications
Frank DiMaio, Institute for Protein Design and Department of Biochemistry, University of Washington
Prof. DiMaio develops and uses computational methods to determine protein structure and design new protein sequences. He is part of the internationally renowned institute of protein design where he is part of the development of the Rosetta suite of tools. Recent research includes using Rosetta to refine CryoEM structures and developing improved methods for protein design.
Publications
A. Keith Dunker, Center for Computational Biology and Bioinformatics, Department of Biochemistry and Molecular Biology, Indiana University Schools of Medicine and Informatics
Prof. Dunker is a pioneer in the study of intrinsically disordered proteins, and played a central role in defining the concept and demonstrating its many important roles in biology, evolution and disease. Key discoveries include defining sequence features for disorder and thereby developing prediction methods, and in demonstrating how intrinsic disorder is pervasive across all domains of life, and in regulating complex biological signaling networks.
Publications
ABSTRACT
Intrinsically disordered proteins and regions (IDPs and IDRs) lack well-defined tertiary structures, yet carry out various important cellular functions, especially those associated with cell signaling and regulation. In eukaryotes, IDPs and IDRs contain the preferred loci for both protein segments encoded by alternatively spliced pre-mRNA (AS) and many post-translational modifications (PTMs). Furthermore, AS and/or PTMs at these loci generally alter the signaling outcomes associated with these IDPs or IDRs. However, the prevalence of such functional modulations remains unknown. Also, the signal-altering mechanisms by which AS, and PTMs modulate function and the extent to which AS and PTMs collaborate in their signaling modulations have not been well defined for particular protein examples. Here we focus on three important signaling and regulatory IDR-containing protein families in humans, namely G-protein coupled receptors (GPCRs), which are transmembrane signaling proteins, the nuclear factors of activated T-cells (NFATs), which are transcription factors (TFs), and the Src family kinases (SFKs), which are signaling enzymes. The goal here is to determine how AS and PTMs individually alter the outcomes of the signaling carried out by the various IDRs and to determine whether AS and PTMs work together to bring about differential cellular responses. We also present data indicating that a wide range of other signaling IDPs or signaling proteins containing IDRs also undergo both AS- and PTM-based modifications, suggesting that these many proteins likely take advantage of signal outcome modulations that result from collaboration among these three features. Hence, we propose that the widespread cooperation of IDPs, AS and/or PTMs substantially contributes to, or even provides the basis for, the vast complexity of eukaryotic cell signaling systems.