A deep understanding of ttie physiology and biophysics of fusion - and its disease relevance - requires a broad and comprehensive approach and relies heavily upon interdisciplinary approaches honed from a decade of studies of the mechanism of viral envelope fusion. These technologies - cell and molecular biology, surface force/adhesion biophysics, and optical imaging.
The specific aims ofthe initial application covered four aspects of SNARE induced fusion: 1) SNARE distribution, mobility, and lateral interactions within the plane ofthe membrane. 2) Adhesive and molecular forces between SNAREs - determinants of transition states and the energetic. 3) Penultimate states of SNARE fusion: capturing the SNAREpin just before lipid-mixing, with a specific focus on the interplay between lipid structure and protein assembly. 4) Protein and lipidic determinants of fusion kinetics and pore formation.
This broad and comprehensive approach to elucidating the mechanism of intracellular membrane fusion by SNARE proteins will deepen our understanding ofthe physiology and biophysics effusion - and its key roles in diabetes.
|Bello, Oscar D; Auclair, Sarah M; Rothman, James E et al. (2016) Using ApoE Nanolipoprotein Particles To Analyze SNARE-Induced Fusion Pores. Langmuir 32:3015-23|
|Xu, Weiming; Nathwani, Bhavik; Lin, Chenxiang et al. (2016) A Programmable DNA Origami Platform to Organize SNAREs for Membrane Fusion. J Am Chem Soc 138:4439-47|
|Li, Feng; Tiwari, Neeraj; Rothman, James E et al. (2016) Kinetic barriers to SNAREpin assembly in the regulation of membrane docking/priming and fusion. Proc Natl Acad Sci U S A 113:10536-41|
|Xu, Weiming; Wang, Jing; Rothman, James E et al. (2015) Accelerating SNARE-Mediated Membrane Fusion by DNA-Lipid Tethers. Angew Chem Int Ed Engl 54:14388-92|
|Li, Feng; KÃ¼mmel, Daniel; Coleman, Jeff et al. (2014) A half-zippered SNARE complex represents a functional intermediate in membrane fusion. J Am Chem Soc 136:3456-64|
|Zorman, Sylvain; Rebane, Aleksander A; Ma, Lu et al. (2014) Common intermediates and kinetics, but different energetics, in the assembly of SNARE proteins. Elife 3:e03348|
|Shi, Lei; Howan, Kevin; Shen, Qing-Tao et al. (2013) Preparation and characterization of SNARE-containing nanodiscs and direct study of cargo release through fusion pores. Nat Protoc 8:935-48|
|Shi, Lei; Shen, Qing-Tao; Kiel, Alexander et al. (2012) SNARE proteins: one to fuse and three to keep the nascent fusion pore open. Science 335:1355-9|
|KÃ¼mmel, Daniel; Krishnakumar, Shyam S; Radoff, Daniel T et al. (2011) Complexin cross-links prefusion SNAREs into a zigzag array. Nat Struct Mol Biol 18:927-33|
|Shen, Jingshi; Rathore, Shailendra S; Khandan, Lavan et al. (2010) SNARE bundle and syntaxin N-peptide constitute a minimal complement for Munc18-1 activation of membrane fusion. J Cell Biol 190:55-63|
Showing the most recent 10 out of 24 publications