title: Phosphorylation-Induced Mechanical Regulation of Intrinsically Disordered Neurofilament Proteins.
abstract: The biological function of protein assemblies has been conventionally equated with a unique three-dimensional protein structure and protein-specific interactions. However, in the past 20 years it has been found that some assemblies contain long flexible regions that adopt multiple structural conformations. These include neurofilament proteins that constitute the stress-responsive supportive network of neurons. Herein, we show that the macroscopic properties of neurofilament networks are tuned by enzymatic regulation of the charge found on the flexible protein regions. The results reveal an enzymatic (phosphorylation) regulation of macroscopic properties such as orientation, stress response, and expansion in flexible protein assemblies. Using a model that explains the attractive electrostatic interactions induced by enzymatically added charges, we demonstrate that phosphorylation regulation is far richer and versatile than previously considered.
authors.affiliation: Raymond and Beverly Sackler School of Physics and Astronomy, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Eti
authors.initials: E
authors.lastname: Malka-Gibor
authors.affiliation: Raymond and Beverly Sackler School of Physics and Astronomy, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Micha
authors.initials: M
authors.lastname: Kornreich
authors.affiliation: Raymond and Beverly Sackler School of Physics and Astronomy, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Laser-Azogui
authors.affiliation: Raymond and Beverly Sackler School of Physics and Astronomy, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Doron
authors.affiliation: Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Irena
authors.initials: I
authors.lastname: Zingerman-Koladko
authors.affiliation: Department of Biochemistry, University of Zurich, Zurich, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Harapin
authors.affiliation: Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University, Beer-Sheva, Israel; Department of Biochemistry, University of Zurich, Zurich, Switzerland.
authors.forename: Ohad
authors.initials: O
authors.lastname: Medalia
authors.affiliation: Raymond and Beverly Sackler School of Physics and Astronomy, Tel Aviv University, Tel Aviv, Israel. Electronic address: roy@post.tau.ac.il.
authors.forename: Roy
authors.initials: R
authors.lastname: Beck
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002417:Cattle; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000378:metabolism*; D055595:Mechanical Phenomena; D008958:Models, Molecular; D016900:Neurofilament Proteins / Q000737:chemistry* / Q000378:metabolism*; D010766:Phosphorylation; D000072756:Protein Conformation, alpha-Helical
chemical_list: D064267:Intrinsically Disordered Proteins; D016900:Neurofilament Proteins