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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