Mechanics of coupling proton movements to c‐ring rotation in ATP synthase

Abstract

F 1 F 0 ATP synthases generate ATP by a rotary catalytic mechanism in which H + transport is coupled to rotation of an oligomeric ring of c subunits extending through the membrane. Protons bind to and then are released from the aspartyl-61 residue of subunit c at the center of the membrane. Subunit a of the F 0 sector is thought to provide proton access channels to and from aspartyl-61. Here, we summarize new information on the structural organization of Escherichia coli subunit a and the mapping of aqueous-accessible residues in the second, fourth and ¢fth transmembrane helices (TMHs). Aqueous-accessible regions of these helices extend to both the cytoplasmic and periplasmic surface. We propose that aTMH4 rotates to alternately expose the periplasmic or cytoplasmic half-channels to aspartyl-61 of subunit c during the proton transport cycle. The concerted rotation of interacting helices in subunit a and subunit c is proposed to be the mechanical force driving rotation of the c-rotor, using a mechanism akin to meshed gears.

Defining the impact on yeast ATP synthase of two pathogenic human mitochondrial DNA mutations, T9185C and T9191C

“…Atp6p is a key subunit of the F O proton-translocating domain of the ATP synthase. Proton movements mediated by Atp6p lead to the rotation of a transmembrane ring of Atp9p subunits (referred to as subunit c in humans) which ends up in conformational changes at the level of the catalytic sites in the F 1 extra-membrane domain of the enzyme that favor the synthesis ATP and its release into the mitochondrial matrix [10,11].…”

Rotating proton pumping ATPases: Subunit/subunit interactions and thermodynamics

“…The rotation enables cooperative interactions between three catalytic sites, each in the b subunits with different conformations. The conformational asymmetry of the three b subunits was suggested biochemically by affinity labeling, chemical crosslinking, and reconstitution from isolated subunits, as reviewed previously (1)(2)(3)(4)(5). The first high-resolution X-ray structure of the F 1 sector from bovine heart mitochondria clearly showed that the three b subunits in F 1 have different catalytic site conformations (7).…”

“…We focus mainly on E. coli F-ATPase rotational catalysis, taking advantage of its easy purification (21), and the accumulated biochemical results for the wild-type and mutant enzymes (2)(3)(4)(5). It should be noted that this enzyme can be studied thermodynamically in the physiological temperature range (10-40 C) of the organism.…”

“…A series of single molecule studies (Table 1) on thermophilic Bacillus PS3 and the Escherichia coli enzyme established that the c subunit (8,9) and cec 10 (10-12) assembly in F 1 and F-ATPase (F O F 1 ), respectively, rotate relative to a stator assembly. Thus, the rotation of F-ATPase is coupled with continuous proton transport through a water channel formed from subunits a and c, which include proton translocating residues Arg and Asp (or Glu), respectively (3).…”

“…This bacterial enzyme contributes greatly to the understanding of mammalian or plant F-ATPases, as it is similar in structure and function to those from mitochondria or chloroplasts. We refer the readers to recent review articles (1)(2)(3)(4)(5) because the length of this article is limited.…”