title: Macromolecular and Small Molecular Crowding Have Similar Effects on α-Synuclein Structure.
abstract: The intracellular milieu contains upwards of 400 g of macromolecules per liter. This crowding is thought to have a larger influence on intrinsically disordered proteins, whose chains are expanded, than on compact globular proteins. Classic theories of macromolecular crowding predict that increasing excluded volume effects will lead disordered proteins to compaction, and a great deal of data, from both simulation and experiments support this idea. We used nuclear magnetic resonance, circular dichroism, and fluorescence spectroscopies to characterize the structure and fibrillation of α-synuclein, an intrinsically disordered protein implicated in Parkinson's disease, using Ficoll70, its monomer sucrose and bovine serum albumin as crowding agents. Surprisingly, volume exclusion induced by high concentrations of macromolecules may not be the main reason for the compaction of α-synuclein. Our results indicate that all aspects crowding must be considered to understand protein conformation under crowded conditions.
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071, P. R. China.|Graduate University of Chinese Academy of Sciences, Beijing, 100029, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Bai
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071, P. R. China.
authors.forename: Maili
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Department of Biochemistry and Biophysics, University of North Carolina-Chapel Hill, Chapel Hill, NC, 27599-3290, USA.
authors.forename: Gary J
authors.identifier: http://orcid.org/0000-0001-6307-542X
authors.initials: GJ
authors.lastname: Pielak
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071, P. R. China.
authors.forename: Conggang
authors.identifier: http://orcid.org/0000-0002-5798-1722
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D046911:Macromolecular Substances / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D011487:Protein Conformation; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013395:Sucrose / Q000737:chemistry*; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D046911:Macromolecular Substances; D054852:Small Molecule Libraries; D051844:alpha-Synuclein; D012710:Serum Albumin, Bovine; D013395:Sucrose
keywords: NMR spectroscopy; circular dichroism; macromolecular crowding; protein structure; α-synuclein