title: Beyond the random coil: stochastic conformational switching in intrinsically disordered proteins.
abstract: Intrinsically disordered proteins (IDPs) participate in critical cellular functions that exploit the flexibility and rapid conformational fluctuations of their native state. Limited information about the native state of IDPs can be gained by the averaging over many heterogeneous molecules that is unavoidable in ensemble approaches. We used single molecule fluorescence to characterize native state conformational dynamics in five synaptic proteins confirmed to be disordered by other techniques. For three of the proteins, SNAP-25, synaptobrevin and complexin, their conformational dynamics could be described with a simple semiflexible polymer model. Surprisingly, two proteins, neuroligin and the NMDAR-2B glutamate receptor, were observed to stochastically switch among distinct conformational states despite the fact that they appeared intrinsically disordered by other measures. The hop-like intramolecular diffusion found in these proteins is suggested to define a class of functionality previously unrecognized for IDPs.
authors.affiliation: Department of Physics, North Carolina State University, Raleigh, NC 27695, USA.
authors.forename: Ucheor B
authors.initials: UB
authors.lastname: Choi
authors.forename: James J
authors.initials: JJ
authors.lastname: McCann
authors.forename: Keith R
authors.initials: KR
authors.lastname: Weninger
authors.forename: Mark E
authors.initials: ME
authors.lastname: Bowen
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D056004:Molecular Dynamics Simulation; D009419:Nerve Tissue Proteins / Q000737:chemistry; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D050683:R-SNARE Proteins / Q000737:chemistry; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry; D015203:Reproducibility of Results; D050825:Synaptosomal-Associated Protein 25 / Q000737:chemistry
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D015816:Cell Adhesion Molecules, Neuronal; C121001:NR2B NMDA receptor; D009419:Nerve Tissue Proteins; D011506:Proteins; D050683:R-SNARE Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; C095992:complexin I; C093438:neuroligin 1