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

Abstract

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.

Curvature Footprints of Transmembrane Proteins in Simulations with the Martini Force Field

“…Similar curvature footprints were obtained in the different membrane compositions used, suggesting that fundamental aspects of protein–lipid interactions (i.e., hydrophobic mismatch) have a predominant role in determining the local curvature environment; however, minor differences arising from varying membrane compositions or enrichment of particular lipids around proteins could be functionally relevant. A number of studies have endeavored to determine the energetics of membrane deformation around curvature-inducing TM proteins. − In general, it has been shown that it is less costly for the membrane to deform than for lipids to redistribute, and although both processes likely occur to varying degrees, the effect of membrane composition on extent of deformation is minor . It is important to note that while the simulations were carried out in a systematic manner, several different approaches were used to obtain the reference data.…”