The machinery of vesicle fusion

The compartmentalization of eukaryotic cells is reliant on the fidelity of vesicle-mediated intracellular transport. Vesicles deliver their cargo via membrane fusion, a process requiring membrane tethers, Sec1/Munc18 (SM) proteins, and SNAREs. These components function in concert to ensure that membrane fusion is efficient and accurate, but the mechanisms underlying their cooperative action are still in many respects mysterious. In this brief review, we highlight recent progress toward a more integrative understanding of the vesicle fusion machinery. We focus particular attention on cryo-electron microscopy structures of intact multisubunit tethers in complex with SNAREs or SM proteins, as well as a structure of an SM protein bound to multiple SNAREs. The insights gained from this work emphasize the advantages of studying the fusion machinery intact and in context.