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Mechanosensitive channels sense mechanical forces in cell membranes and underlie many biological sensing processes.sup.1-3. However, how exactly they sense mechanical force remains under investigation.sup.4. The bacterial mechanosensitive channel of small conductance, MscS, is one of the most extensively studied mechanosensitive channels.sup.4-8, but how it is regulated by membrane tension remains unclear, even though the structures are known for its open and closed states.sup.9-11. Here we used cryo-electron microscopy to determine the structure of MscS in different membrane environments, including one that mimics a membrane under tension. We present the structures of MscS in the subconducting and desensitized states, and demonstrate that the conformation of MscS in a lipid bilayer in the open state is dynamic. Several associated lipids have distinct roles in MscS mechanosensation. Pore lipids are necessary to prevent ion conduction in the closed state. Gatekeeper lipids stabilize the closed conformation and dissociate with membrane tension, allowing the channel to open. Pocket lipids in a solvent-exposed pocket between subunits are pulled out under sustained tension, allowing the channel to transition to the subconducting state and then to the desensitized state. Our results provide a mechanistic underpinning and expand on the 'force-from-lipids' model for MscS mechanosensation.sup.4,11. The authors report the structural characterization of the mechanically activated channel MscS in different membrane environments and show how the mechanosensation of MscS can be visualized., Author(s): Yixiao Zhang [sup.1] , Csaba Daday [sup.2] , Ruo-Xu Gu [sup.2] , Charles D. Cox [sup.3] [sup.4] , Boris Martinac [sup.3] [sup.4] , Bert L. de Groot [sup.2] , [...]

Ribosome biogenesis is a highly complex process in eukaryotes, involving temporally and spatially regulated ribosomal protein (r-protein) binding and ribosomal RNA remodelling events in the nucleolus, nucleoplasm and cytoplasm (1,2). [...]

DNA replication in eukaryotes is strictly regulated by several mechanisms. A central step in this replication is the assembly of the heterohexameric minichromosome maintenance (MCM2-7) helicase complex at replication origins during G1 phase as an inactive double hexamer. Here, using cryo-electron microscopy, we report a near-atomic structure of the MCM2-7 double hexamer purified from yeast G1 chromatin. Our structure shows that two single hexamers, arranged in a tilted and twisted fashion through interdigitated amino-terminal domain interactions, form a kinked central channel. Four constricted rings consisting of conserved interior β-hairpins from the two single hexamers create a narrow passageway that tightly fits duplex DNA. This narrow passageway, reinforced by the offset of the two single hexamers at the double hexamer interface, is flanked by two pairs of gate-forming subunits, MCM2 and MCM5. These unusual features of the twisted and tilted single hexamers suggest a concerted mechanism for the melting of origin DNA that requires structural deformation of the intervening DNA., For DNA to be replicated, two strands of the duplex DNA must be separated so that each can serve as a template for the synthesis of daughter strands. In both [...]