The a-and ,B-subunits of membrane-bound ATP synthase complex bind ATP and ADP: B contributes to catalyic sites, and a may be involved in regulation of ATP synthase activity. The sequences of ,B-subunits are highly conserved in Escherichia coli and bovine mitochondria. Also a and ( are weakly homologous to each other throughout most of their amino acid sequences, suggesting that they have common functions in catalysis. Related sequences in both a and (3 and in other enzymes that bind ATP or ADP in catalysis, notably myosin, phosphofructokinase, and adenylate kinase, help to identify regions contributing to an adenine nucleotide binding fold in both ATP synthase subunits.

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Mitochondria produce most of the energy in animal cells by a process called oxidative phosphorylation. Electrons are passed along a series of respiratory enzyme complexes located in the inner mitochondrial membrane, and the energy released by this electron transfer is used to pump protons across the membrane. The resultant electrochemical gradient enables another complex, adenosine 5'-triphosphate (ATP) synthase, to synthesize the energy carrier ATP. Important new mechanistic insights into oxidative phosphorylation have emerged from recent three-dimensional structural analyses of ATP synthase and two of the respiratory enzyme complexes, cytochrome bc1 and cytochrome c oxidase. This work, and new enzymological studies of ATP synthase's unusual catalytic mechanism, are reviewed here.

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The WW domain is a new protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro. It is present in a number of signalling and regulatory proteins, often in several copies. Here we investigate the solution structure of the WW domain of human YAP65 (for Yes kinase-associated protein) in complex with proline-rich peptides containing the core motif PPxY. The structure of the domain with the bound peptide GTPPPPYTVG is a slightly curved, three-stranded, antiparallel beta-sheet. Two prolines pack against the first tryptophan, forming a hydrophobic buckle on the convex side of the sheet. The concave side has three exposed hydrophobic residues (tyrosine, tryptophan and leucine) which form the binding site for the ligand. A non-conserved isoleucine in the amino-terminal flanking region covers a hydrophobic patch and stabilizes the WW domain of human YAP65 in vitro. The structure of the WW domain differs from that of the SH3 domain and reveals a new design for a protein module that uses stacked aromatic surface residues to arrange a binding site for proline-rich peptides.

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Phosphatidylinositol bisphosphate has been found to bind specifically to pleckstrin homology (PH) domains that are commonly present in signalling proteins but also found in cytoskeleton. We have studied the complexes of the beta‐spectrin PH domain and soluble inositol phosphates using both circular dichroism and nuclear magnetic resonance spectroscopy, and X‐ray crystallography. The specific binding site is located in the centre of a positively charged surface patch of the domain. The presence of 4,5‐bisphosphate group on the inositol ring is critical for binding. In the crystal structure that has been determined at 2.0 A resolution, inositol‐1,4,5‐trisphosphate is bound with salt bridges and hydrogen bonds through these phosphate groups whereas the 1‐phosphate group is mostly solvent‐exposed and the inositol ring has virtually no interactions with the protein. We propose a model in which PH domains are involved in reversible anchoring of proteins to membranes via their specific binding to phosphoinositides. They could also participate in a response to a second messenger such as inositol trisphosphate, organizing cross‐roads in cellular signalling.

This article tries to be a compact summary of some recent research on cytochromecoxidase (EC 1.9.3.1), an important enzyme in membrane bioenergetics. Cytochrome oxidase is the terminal catalyst of the mitochondrial respiratory chain. It uses the electrons flowing through the chain to reduce oxygen molecules to water. Four electrons and four protons are consumed in the reduction of O2to two molecules of water (Fig. 1). Cytochrome oxidase contains four redoxactive metal centres. Two of these are copper atoms, two haem A groups. These four centres are employed in the dioxygen-binding site and in the electron-transferring pathways from cytochromec. The enzyme is also called cytochromeaa3, because the protein-bound haems are functionally and spectroscopically different.