title: Lipid Regulated Intramolecular Conformational Dynamics of SNARE-Protein Ykt6.
abstract: Cellular informational and metabolic processes are propagated with specific membrane fusions governed by soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNARE). SNARE protein Ykt6 is highly expressed in brain neurons and plays a critical role in the membrane-trafficking process. Studies suggested that Ykt6 undergoes a conformational change at the interface between its longin domain and the SNARE core. In this work, we study the conformational state distributions and dynamics of rat Ykt6 by means of single-molecule Förster Resonance Energy Transfer (smFRET) and Fluorescence Cross-Correlation Spectroscopy (FCCS). We observed that intramolecular conformational dynamics between longin domain and SNARE core occurred at the timescale ~200 μs. Furthermore, this dynamics can be regulated and even eliminated by the presence of lipid dodecylphoshpocholine (DPC). Our molecular dynamic (MD) simulations have shown that, the SNARE core exhibits a flexible structure while the longin domain retains relatively stable in apo state. Combining single molecule experiments and theoretical MD simulations, we are the first to provide a quantitative dynamics of Ykt6 and explain the functional conformational change from a qualitative point of view.
authors: Department of Physics, Fudan University, 200433, Shanghai, P.R. China.|State Key Laboratory of Surface Physics, Fudan University, 200433, Shanghai, P.R. China.
authors: Yawei
authors: Y
authors: Dai
authors: Institute of Biophysics, Goethe-University Frankfurt Max-von-Laue-Str. 1, 60438, Frankfurt/Main, Germany.
authors: Markus
authors: M
authors: Seeger
authors: Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, 220 Handan Rd., 200433, Shanghai, P.R. China.
authors: Jingwei
authors: J
authors: Weng
authors: Department of Physics, Fudan University, 200433, Shanghai, P.R. China.|State Key Laboratory of Surface Physics, Fudan University, 200433, Shanghai, P.R. China.
authors: Song
authors: S
authors: Song
authors: Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, 220 Handan Rd., 200433, Shanghai, P.R. China.
authors: Wenning
authors: W
authors: Wang
authors: Department of Physics, Fudan University, 200433, Shanghai, P.R. China.|State Key Laboratory of Surface Physics, Fudan University, 200433, Shanghai, P.R. China.
authors: Yan-Wen
authors: YW
authors: Tan
mesh_terms: D000818:Animals; D001059:Apoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D015870:Gene Expression; D007700:Kinetics; D008561:Membrane Fusion; D056004:Molecular Dynamics Simulation; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D050683:R-SNARE Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000072760:Single Molecule Imaging; D013816:Thermodynamics
chemical_list: D001059:Apoproteins; D050683:R-SNARE Proteins; D011994:Recombinant Proteins; C491481:Ykt6 protein, rat; D010767:Phosphorylcholine; C028810:dodecylphosphocholine