Disordered Motifs and Domains in Cell Control - October 11-15, 2014

Disordered Motifs and Domains in Cell Control

Sunday Speaker Abstracts

Structural Biology of Disordered Motifs in Regulation of Apoptosis and Cell Division Ariele V. Follis 1 , Jerry Chipuk 2 , Fabien Llambi 3 , James Asciolla 2 ,Yongqi Huang 1 , Mi-Kyung Yoon 1 , Steve Otieno 1 , Moreno Lelli 4 , Mi-Kyung Yun, Max Tsytlonok 5 , Hugo Sanabria 6 , Yuefeng Wang 1 , Brett Waddell 1 , Cheon-Gil Park 1 , Siva Vaithiyalingam 1 , Diana M. Mitrea 1 , Stephen W. White 1 , Peter Tompa 5,7 , Claus Seidel 6 , Doug Green 2 , Richard W. Kriwacki 1,8 Departments of 1 Structural Biology, and 3 Immunology, St. Jude Children’s Research Hospital, USA; 2 Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4 Centre de RMN à Très Hauts Champs, France; 5 VIB Structural Biology Research Center (SBRC), Vrije Universiteit Brussel, Brussels 1050, Belgium; 6 Institut für Physikalische Chemie, Lehrstuhl für Molekulare Physikalische Chemie, Heinrich-Heine- Universität, Düsseldorf, Germany; 7 Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest 1519, Hungary; 8 Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Sciences Center, Memphis, TN, USA. Conserved linear motifs frequently occur within disordered regions of proteins and, through interactions with other biomolecules (e.g., proteins, nucleic acids, lipids, metabolites, etc.), contribute to function in myriad biological processes. Our studies have shown that dynamics within motifs, both in their free states and when bound to their functional targets, are critical for the transmission of signals within regulatory pathways. In particular, posttranslational modifications serve to switch motif function by altering their interactions. We will describe the roles of dynamic, disordered motifs in regulation of apoptosis and cell division. Studies of a disordered motif in p53 have revealed the roles of posttranslational modifications in mediating interactions with and activation of the apoptotic effector, BAX. Studies of the cell cycle regulators, p21 and p27, have shown i) that motif dynamics within functional complexes is critical for signal transmission, and ii) that subtle differences in motif topology can lead to dramatic differences in regulatory behavior. Our studies illustrate the structural, dynamic, and functional complexities of motifs within disordered regions of proteins and, in general, advance our understanding of disorder-function relationships for proteins.

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