Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Intrinsically Disordered Proteins, Alternative Splicing, and Post-translational Modification (IDP-AS-PTM): A Toolkit for Developmental Biology

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.

Keith Dunker

Center for Computational Biology and Bioinformatics
Department of Biochemistry and Molecular Biology
Indiana University Schools of Medicine and Informatics
Indianapolis, IN 46202, USA

Email: kedunker@iu.edu