TY - JOUR AB - The mitochondrial respiratory chain, formed by five protein complexes, utilizes energy from catabolic processes to synthesize ATP. Complex I, the first and the largest protein complex of the chain, harvests electrons from NADH to reduce quinone, while pumping protons across the mitochondrial membrane. Detailed knowledge of the working principle of such coupled charge-transfer processes remains, however, fragmentary due to bottlenecks in understanding redox-driven conformational transitions and their interplay with the hydrated proton pathways. Complex I from Thermus thermophilus encases 16 subunits with nine iron–sulfur clusters, reduced by electrons from NADH. Here, employing the latest crystal structure of T. thermophilus complex I, we have used microsecond-scale molecular dynamics simulations to study the chemo-mechanical coupling between redox changes of the iron–sulfur clusters and conformational transitions across complex I. First, we identify the redox switches within complex I, which allosterically couple the dynamics of the quinone binding pocket to the site of NADH reduction. Second, our free-energy calculations reveal that the affinity of the quinone, specifically menaquinone, for the binding-site is higher than that of its reduced, menaquinol form—a design essential for menaquinol release. Remarkably, the barriers to diffusive menaquinone dynamics are lesser than that of the more ubiquitous ubiquinone, and the naphthoquinone headgroup of the former furnishes stronger binding interactions with the pocket, favoring menaquinone for charge transport in T. thermophilus. Our computations are consistent with experimentally validated mutations and hierarchize the key residues into three functional classes, identifying new mutation targets. Third, long-range hydrogen-bond networks connecting the quinone-binding site to the transmembrane subunits are found to be responsible for proton pumping. Put together, the simulations reveal the molecular design principles linking redox reactions to quinone turnover to proton translocation in complex I. AU - Gupta, Chitrak AU - Khaniya, Umesh AU - Chan, Chun Kit AU - Dehez, Francois AU - Shekhar, Mrinal AU - Gunner, M. R. AU - Sazanov, Leonid A AU - Chipot, Christophe AU - Singharoy, Abhishek ID - 8040 IS - 20 JF - Journal of the American Chemical Society SN - 00027863 TI - Charge transfer and chemo-mechanical coupling in respiratory complex I VL - 142 ER - TY - JOUR AB - We introduce a self-propelled colloidal hematite docker that can be steered to a small particle cargo many times its size, dock, transport the cargo to a remote location, and then release it. The self-propulsion and docking are reversible and activated by visible light. The docker can be steered either by a weak uniform magnetic field or by nanoscale tracks in a textured substrate. The light-activated motion and docking originate from osmotic/phoretic particle transport in a concentration gradient of fuel, hydrogen peroxide, induced by the photocatalytic activity of the hematite. The docking mechanism is versatile and can be applied to various materials and shapes. The hematite dockers are simple single-component particles and are synthesized in bulk quantities. This system opens up new possibilities for designing complex micrometer-size factories as well as new biomimetic systems. AU - Palacci, Jérémie A AU - Sacanna, Stefano AU - Vatchinsky, Adrian AU - Chaikin, Paul M. AU - Pine, David J. ID - 9167 IS - 43 JF - Journal of the American Chemical Society KW - Colloid and Surface Chemistry KW - Biochemistry KW - General Chemistry KW - Catalysis SN - 00027863 TI - Photoactivated colloidal dockers for cargo transportation VL - 135 ER -