The Phylogenetic Signature Underlying ATP Synthase c-Ring Compliance

Area of Science:

• Biochemistry and Molecular Biophysics
• Bioenergetics
• Structural Biology

Background:

• The proton-driven ATP synthase (FOF1) is a molecular machine that synthesizes ATP.
• Its function relies on the coordinated rotation of its FO and F1 components, coupled by an elastic power transmission.
• The FO c-ring is a key component of the rotor module, where proton transport is coupled to rotation.

Purpose of the Study:

• To computationally investigate the contribution of the FO c-ring to the overall elastic compliance of ATP synthase.
• To identify the molecular determinants responsible for the c-ring's mechanical properties and their role in proton-driven rotation.

Main Methods:

• Principal component analysis (PCA) of conformational ensembles derived from bovine mitochondrial c-ring X-ray structure.
• Covariance analysis of residue coevolution and structural-alphabet-based local dynamics correlations.
• Analysis of monomer and dimer ensembles extracted from complete c-rings.

Main Results:

• The FO c-ring contributes to the measured elastic compliance, primarily through angular rotary twist.
• Ring rotation is coupled to the rotation of external helices within individual c-subunits.
• The hinge for rotation involves the proton-binding site and the IB-GGGG motif, with couplings linking collective ring and subunit motions.
• Coevolution analysis revealed subunit architecture and identified dynamic couplings underlying rotary and bending motions.

Conclusions:

• The FO c-ring is a significant contributor to ATP synthase's elastic compliance.
• Specific motifs, including the proton-binding site and IB-GGGG, act as hinges for rotation.
• The identified dynamics and couplings are crucial for linking proton transfer to mechanical rotation and ATP synthesis.