SNARE-ing the structures of Sec1/Munc18 proteins

•Sec1/Munc18 (SM) proteins are essential for SNARE-mediated membrane fusion.•All SM proteins characterized to date have three domains organized into an arch-shape.•SM proteins are dynamic: domain 1 rotates by ∼50° and domain 3a bends by ∼180°.•Three binding sites for partner proteins have been characterized structurally.•How the highly plastic SM proteins regulate membrane fusion remains a mystery? Membrane fusion is essential for cellular transport in eukaryotes. Abnormalities contribute to a wide range of diseases including diabetes and neurological disorders. A key regulator of SNARE-mediated membrane fusion is the Sec1/Munc18 (SM) protein family. Universal structural features of SM proteins have been identified that affect the way these interact with their partner Syntaxin SNARE proteins. Whilst the molecular basis for SM-regulated SNARE complex formation has been extensively studied, it remains poorly understood. Recent crystal structures of SM proteins alone or in complex have provided new insight. Here we examine the available structural information on SM proteins for clues to how these enigmatic proteins might regulate SNARE complex assembly and membrane fusion.