title: Allosteric switch regulates protein-protein binding through collective motion.
abstract: Many biological processes depend on allosteric communication between different parts of a protein, but the role of internal protein motion in propagating signals through the structure remains largely unknown. Through an experimental and computational analysis of the ground state dynamics in ubiquitin, we identify a collective global motion that is specifically linked to a conformational switch distant from the binding interface. This allosteric coupling is also present in crystal structures and is found to facilitate multispecificity, particularly binding to the ubiquitin-specific protease (USP) family of deubiquitinases. The collective motion that enables this allosteric communication does not affect binding through localized changes but, instead, depends on expansion and contraction of the entire protein domain. The characterization of these collective motions represents a promising avenue for finding and manipulating allosteric networks.
authors.affiliation: Department for Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany; Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany; colin.smith@mpibpc.mpg.de cigr@nmr.mpibpc.mpg.de donghan.lee@louisville.edu bgroot@gwdg.de.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Smith
authors.affiliation: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany; Department of Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202.
authors.forename: David
authors.identifier: http://orcid.org/0000-0002-4993-7983
authors.initials: D
authors.lastname: Ban
authors.affiliation: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany;
authors.forename: Supriya
authors.initials: S
authors.lastname: Pratihar
authors.affiliation: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany;
authors.forename: Karin
authors.initials: K
authors.lastname: Giller
authors.affiliation: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany;
authors.forename: Maria
authors.initials: M
authors.lastname: Paulat
authors.affiliation: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany;
authors.forename: Stefan
authors.initials: S
authors.lastname: Becker
authors.affiliation: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany; colin.smith@mpibpc.mpg.de cigr@nmr.mpibpc.mpg.de donghan.lee@louisville.edu bgroot@gwdg.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Griesinger
authors.affiliation: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany; Department of Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202 colin.smith@mpibpc.mpg.de cigr@nmr.mpibpc.mpg.de donghan.lee@louisville.edu bgroot@gwdg.de.
authors.forename: Donghan
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department for Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany; colin.smith@mpibpc.mpg.de cigr@nmr.mpibpc.mpg.de donghan.lee@louisville.edu bgroot@gwdg.de.
authors.forename: Bert L
authors.initials: BL
authors.lastname: de Groot
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D011506:Proteins
keywords: allostery; concerted motion; nuclear magnetic resonance; protein dynamics; relaxation dispersion