Recent advances in structure-functional studies of mitochondrial factor B

Abstract

Since the early studies on the resolution and reconstitution of the oxidative phosphorylation system from animal mitochondria, coupling factor B was recognized as an essential component of the machinery responsible for energy-driven ATP synthesis. At the phenomenological level, factor B was agreed to lie at the interface of energy transfer between the respiratory chain and the ATP synthase complex. However, biochemical characterization of the factor B polypeptide has proved difficult. It was not until 1990 that the N-terminal amino acid sequence of bovine mitochondrial factor B was reported, which followed, a decade later, by the report describing the amino acid sequence of full-length human factor B and its functional characterization. The present review summarizes the recent advances in structure-functional studies of factor B, including its recently determined crystal structure at 0.96 A resolution. Ectopic expression of human factor B in cultured animal cells has unexpectedly revealed its role in shaping mitochondrial morphology. The supramolecular assembly of ATP synthase as dimer ribbons at highly curved apices of the mitochondrial cristae was recently suggested to optimize ATP synthesis under proton-limited conditions. We propose that the binding of the ATP synthase dimers with factor B tetramers could be a means to enhance the efficiency of the terminal step of oxidative phosphorylation in animal mitochondria.

Figure 1. Ribbon model of the crystal structure of a bovine factor B Gly3-Glu mutant refined to a 0.96 Å resolution (PDB code 3e4g)

The figure depicts the factor B molecule viewed head-on from the N-terminal domain. N and C indicate the NH₂- and COOH-termini of the polypeptide. The side chains of Phe1, Trp2, Trp4, Phe9, as well as Cys33, Cys71, Cys92, Cys94, and Cys123 are shown in ball-and-stick presentation. Cys101, which is located at the convex side of the protein, is not indicated. The N-terminal α-helix is proposed to anchor factor B to the matrix side of the mitochondrial inner membrane, thus orienting the rest of the polypeptide molecule in a lateral direction along the membrane surface. The depth of the α-helix insertion into the membrane is yet to be determined. For clarity, the tightly bound Mg⁺⁺ ion is omitted. F, phenylalanine; W, tryptophan; C, cysteine. The figure was prepared with ICM Browser Pro software (Molsoft L.L.C., La Jolla, CA).