Assembly and disassembly of SNAREs in membrane fusion.
All life processes are governed at the chemical level and therefore knowledge of how single molecules interact provides a fundamental understanding of Nature. An aspect of molecular interactions, is the self-assembly of supramolecular structures. Membrane fusion for example, the very fundamental of life process requires the assembly and disassembly of a supramolecular complex, formed when certain proteins in opposing bilayers meet. Membrane fusion is essential for numerous cellular activities, including hormone secretion, enzyme release, and neurotransmission. In living cells, membrane fusion is mediated via a specialized set of proteins present in opposing bilayers. Target membrane proteins, SNAP-25 and syntaxin (t-SNAREs), and secretory vesicle-associated protein (v-SNARE) are part of the conserved protein complex involved in fusion of opposing lipid membranes. The structure and arrangement of membrane-associated full length SNARE complex, was first examined using atomic force microscopy (AFM). Results from the study demonstrate that t-SNAREs and v-SNARE, when present in opposing bilayers, interact in a circular array to form supramolecular ring complexes each measuring a few nanometers. The size of the ring complex is directly proportional to the curvature of the opposing bilayers. In the presence of calcium, the ring-complex helps in establishing continuity between the opposing bilayers. In contrast, in the absence of membrane, soluble v- and t-SNAREs fail to assemble in such specific and organized pattern, nor form such conducting channels. Once v-SNARE and t-SNAREs residing in opposing bilayers meet, the resulting SNARE complex overcome the repulsive forces between opposing bilayers, bringing them closer to within a distance of 2.8-3 A, allowing calcium bridging of the opposing phospholipids head groups, leading to local dehydration and membrane fusion.
Jena
Bhanu P
BP
Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000538:Aluminum Silicates; D001671:Biochemistry / Q000379:methods*; D002942:Circular Dichroism; D055724:Electrophysiological Phenomena; D008051:Lipid Bilayers / Q000378:metabolism; D008561:Membrane Fusion; D018625:Microscopy, Atomic Force; D017433:Protein Structure, Secondary; D050600:SNARE Proteins / Q000737:chemistry / Q000378:metabolism*; D013499:Surface Properties; D014961:X-Ray Diffraction
D000538:Aluminum Silicates; D008051:Lipid Bilayers; D050600:SNARE Proteins; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C011934:mica