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Rotation of the c-Ring Promotes the Curvature Sorting of Monomeric ATP Synthases

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ATP synthases are proteins that catalyse the formation of ATP through the rotatory movement of their membrane-spanning subunit. In mitochondria, ATP synthases are found to arrange as dimers at the high-curved edges of cristae. Here, a direct link is explored between the rotatory movement of ATP synthases and their preference for curved membranes. An active curvature sorting of ATP synthases in lipid nanotubes pulled from giant vesicles is found. Coarse-grained simulations confirm the curvature-seeking behaviour of rotating ATP synthases, promoting reversible and frequent protein-protein contacts. The formation of transient protein dimers relies on the membrane-mediated attractive interaction of the order of 1.5 kBT produced by a hydrophobic mismatch upon protein rotation. Transient dimers are sustained by a conic-like arrangement characterized by a wedge angle of θ ≈ 50°, producing a dynamic coupling between protein shape and membrane curvature. The results suggest a new role of the rotational movement of ATP synthases for their dynamic self-assembly in biological membranes.

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Funding Information: D.V.G. and M.M. contributed equally to this work and are co‐first authors. I.L.‐M. and M.P.L. acknowledge financial support from the Spanish Ministry of Science, Innovation and Universities through the grant PGC2018‐097903‐B‐I00. This work was also supported by the TECNOLOGÍAS 2018 program funded by the Regional Government of Madrid (Grant S2018/BAA‐4403 SINOXPHOS‐CM) and PID2021‐125024NB‐C22 (To I.L.‐M.). DVG thanks the Regional Government of Madrid for an assistant researcher contract (CT103/19/PEJ‐2019‐AI/IND‐13687). M.M. acknowledges Fundação para a Ciência e a Tecnologia's (FCT) fellowship SPRH/BD/128290/2017. M.N.M. acknowledges financial support from FCT for fellowship CEECIND/04124/2017 and project MOSTMICRO‐ITQB, with references UIDB/04612/2020 and UIDP/04612/2020. F.J.C.‐G. was supported by the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund through grant RTI2018‐095802‐B‐I00. V.G.A.‐V. thanks the Regional Government of Madrid, Universidad Complutense de Madrid and Fundación Complutense for computational resources (by Grant PR27/21 030). I.L.‐M. thanks Dr. Frédéric Pincet and Dr. Paolo Natale for fruitful discussions. Publisher Copyright: © 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

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E.coli FF ATP synthase giant vesicles lipid nanotubes micromanipulation Medicine (miscellaneous) General Chemical Engineering General Materials Science Biochemistry, Genetics and Molecular Biology (miscellaneous) General Engineering General Physics and Astronomy

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