Investigating the Role of Large-Scale Domain Dynamics in Protein-Protein Interactions.
Intrinsically disordered linkers provide multi-domain proteins with degrees of conformational freedom that are often essential for function. These highly dynamic assemblies represent a significant fraction of all proteomes, and deciphering the physical basis of their interactions represents a considerable challenge. Here we describe the difficulties associated with mapping the large-scale domain dynamics and describe two recent examples where solution state methods, in particular NMR spectroscopy, are used to investigate conformational exchange on very different timescales.
Institut de Biologie Structurale, CEA, Centre National de la Recherche Scientifique, University Grenoble Alpes Grenoble, France.
Elise
E
Delaforge
Institut de Biologie Structurale, CEA, Centre National de la Recherche Scientifique, University Grenoble Alpes Grenoble, France.
Sigrid
S
Milles
Institut de Biologie Structurale, CEA, Centre National de la Recherche Scientifique, University Grenoble Alpes Grenoble, France.
Jie-Rong
JR
Huang
Institut de Biologie Structurale, CEA, Centre National de la Recherche Scientifique, University Grenoble Alpes Grenoble, France.
Denis
D
Bouvier
Institut de Biologie Structurale, CEA, Centre National de la Recherche Scientifique, University Grenoble Alpes Grenoble, France.
Malene Ringkjøbing
MR
Jensen
Institute of Structural Biology, Helmholtz Zentrum MünchenNeuherberg, Germany; Center for Integrated Protein Science Munich at Biomolecular NMR, Technische Universität MünchenGarching, Germany.
Michael
M
Sattler
Institut de Biologie Structurale, CEA, Centre National de la Recherche Scientifique, University Grenoble Alpes Grenoble, France.
Darren J
DJ
Hart
Institut de Biologie Structurale, CEA, Centre National de la Recherche Scientifique, University Grenoble Alpes Grenoble, France.
Martin
M
Blackledge
chemical exchange saturation transfer (CEST); conformational dynamics; free-energy landscape; multi-domain proteins; nuclear magnetic resonance (NMR); single molecule Förster resonance energy transfer (FRET); small angle scattering
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