SNARE assembly and disassembly exhibit a pronounced hysteresis.
SNARE proteins are essential for intracellular membrane fusion of eukaryotes. Their assembly into stable four-helix bundles bridges membranes and may provide the energy for initiating membrane fusion. In vitro, assembly of soluble SNARE fragments is accompanied by major structural rearrangements that can be described as a folding reaction. The pathways and the thermodynamics of SNARE protein interactions, however, are not known. Here we report that assembly and dissociation of two distantly related SNARE complexes exhibit a marked hysteresis. The assembled and disassembled native states are separated by a kinetic barrier and cannot equilibrate on biologically relevant timescales. We suggest that the hysteresis is a hallmark of all SNARE complexes and that complex assembly and disassembly follow different pathways that may be independently controlled.
Fasshauer
Dirk
D
Department of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, AM Fassberg 11, 37077 Göttingen, Germany. dfassha@mpibpc.gwdg.de
Antonin
Wolfram
W
Subramaniam
Vinod
V
Jahn
Reinhard
R
D002942:Circular Dichroism; D004591:Electrophoresis, Polyacrylamide Gel; D011992:Endosomes / Q000737:chemistry; D019791:Guanidine / Q000494:pharmacology; D007700:Kinetics; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D011489:Protein Denaturation / Q000187:drug effects; D017510:Protein Folding; D017433:Protein Structure, Secondary / Q000187:drug effects; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D013569:Synapses / Q000737:chemistry; D050825:Synaptosomal-Associated Protein 25; D013696:Temperature; D013816:Thermodynamics; D014508:Urea / Q000494:pharmacology; D033921:Vesicular Transport Proteins
D046911:Macromolecular Substances; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D050825:Synaptosomal-Associated Protein 25; D033921:Vesicular Transport Proteins; D014508:Urea; D019791:Guanidine