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Science 324 (5924): 198-203

Copyright © 2009 by the American Association for the Advancement of Science

Sending Signals Dynamically

Robert G. Smock, and Lila M. Gierasch

Abstract: Proteins mediate transmission of signals along intercellular and intracellular pathways and between the exterior and the interior of a cell. The dynamic properties of signaling proteins are crucial to their functions. We discuss emerging paradigms for the role of protein dynamics in signaling. A central tenet is that proteins fluctuate among many states on evolutionarily selected energy landscapes. Upstream signals remodel this landscape, causing signaling proteins to transmit information to downstream partners. New methods provide insight into the dynamic properties of signaling proteins at the atomic scale. The next stages in the signaling hierarchy—how multiple signals are integrated and how cellular signaling pathways are organized in space and time—present exciting challenges for the future, requiring bold multidisciplinary approaches.

Department of Biochemistry and Molecular Biology and Department of Chemistry, University of Massachusetts, Amherst, MA 01003, USA. E-mail: gierasch{at} (L.M.G.); rsmock{at} (R.G.S.)

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Mol Syst Biol 6, 414
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Capturing cooperative interactions with the PSI-MI format.
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Database 2013, bat066
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PNAS 110, 14231-14236
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Peptide Modulation of Class I Major Histocompatibility Complex Protein Molecular Flexibility and the Implications for Immune Recognition.
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J. Biol. Chem. 288, 24372-24381
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Protein Conformational Diversity Correlates with Evolutionary Rate.
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Mol. Biol. Evol. 30, 1500-1503
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Rapid Evolutionary Dynamics of Structural Disorder as a Potential Driving Force for Biological Divergence in Flaviviruses.
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Genome Biol Evol 5, 504-513
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Structural Factors That Determine Selectivity of a High Fidelity DNA Polymerase for Deoxy-, Dideoxy-, and Ribonucleotides.
W. Wang, E. Y. Wu, H. W. Hellinga, and L. S. Beese (2012)
J. Biol. Chem. 287, 28215-28226
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p38{gamma} Mitogen-activated Protein Kinase Signals through Phosphorylating Its Phosphatase PTPH1 in Regulating Ras Protein Oncogenesis and Stress Response.
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J. Biol. Chem. 287, 27895-27905
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Mechanistic Insights into the Retaining Glucosyl-3-phosphoglycerate Synthase from Mycobacteria.
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PNAS 109, 6078-6083
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Agonism/antagonism switching in allosteric ensembles.
H. N. Motlagh and V. J. Hilser (2012)
PNAS 109, 4134-4139
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Conserved, Disordered C Terminus of DnaK Enhances Cellular Survival upon Stress and DnaK in Vitro Chaperone Activity.
R. G. Smock, M. E. Blackburn, and L. M. Gierasch (2011)
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Dynamic fluctuations lubricate the circadian clock.
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PNAS 108, 14377-14378
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Coevolutionary Analysis Enabled Rational Deregulation of Allosteric Enzyme Inhibition in Corynebacterium glutamicum for Lysine Production.
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Mapping allostery through the covariance analysis of NMR chemical shifts.
R. Selvaratnam, S. Chowdhury, B. VanSchouwen, and G. Melacini (2011)
PNAS 108, 6133-6138
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The Intrinsically Disordered Nuclear Localization Signal and Phosphorylation Segments Distinguish the Membrane Affinity of Two Cytidylyltransferase Isoforms.
M. K. Dennis, S. G. Taneva, and R. B. Cornell (2011)
J. Biol. Chem. 286, 12349-12360
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Phospho.ELM: a database of phosphorylation sites--update 2011.
H. Dinkel, C. Chica, A. Via, C. M. Gould, L. J. Jensen, T. J. Gibson, and F. Diella (2011)
Nucleic Acids Res. 39, D261-D267
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PCDB: a database of protein conformational diversity.
E. I. Juritz, S. F. Alberti, and G. D. Parisi (2011)
Nucleic Acids Res. 39, D475-D479
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Periplasmic domain of the sensor-kinase BvgS reveals a new paradigm for the Venus flytrap mechanism.
J. Herrou, C. Bompard, R. Wintjens, E. Dupre, E. Willery, V. Villeret, C. Locht, R. Antoine, and F. Jacob-Dubuisson (2010)
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An Ensemble View of Allostery.
V. J. Hilser (2010)
Science 327, 653-654
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PNAS 107, 2007-2012
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ELM: the status of the 2010 eukaryotic linear motif resource.
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Nucleic Acids Res. 38, D167-D180
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Structural basis of activation-dependent binding of ligand-mimetic antibody AL-57 to integrin LFA-1.
H. Zhang, J.-h. Liu, W. Yang, T. Springer, M. Shimaoka, and J.-h. Wang (2009)
PNAS 106, 18345-18350
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The Vitamin D Sterol-Vitamin D Receptor Ensemble Model Offers Unique Insights into Both Genomic and Rapid-Response Signaling.
M. T. Mizwicki and A. W. Norman (2009)
Science Signaling 2, re4
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