Metal-binding sites in proteins.

A dramatic increase in the number of solved metalloprotein structures and recent breakthroughs in structural analysis have provided a sufficiently detailed understanding of the structural chemistry of some metal-binding sites to allow successful design. As a result, metal-binding site design is now one of the most powerful and promising approaches for influencing protein folding, assembly, stability and catalysis.     

Combinations of turns in proteins.

We observed that beta- and gamma-turns in protein structure may be associated as peptides representing combinations of turns that span between nine and 26 amino acid residues along the polypeptide backbone chain and often correspond to loops in the protein structure. Around 475 peptides resulted from the analysis of a non-redundant data set corresponding to 248 protein crystal structures selected from the Protein Data Bank. Nearly 40% protein chains are associated with two or more peptides and the peptides with nine and 10 amino acid residues are more frequent. A maximum of four distinct peptides varying in number of amino acid residues were observed in at least 10 proteins along the same protein chain. Nearly 80% peptides comprise type IV beta-turns that are associated with irregular dihedral angle values suggesting this may be important for the conformational diversity associated with the loops in proteins. In general, predominant interactions that possibly stabilize these peptides involve main-chain and side-chain interactions with solvent, in addition to hydrogen bond, salt-bridge and non-bonded interactions. Majority of the peptides were observed in hydrolase, oxidoreductase, transferase, serine proteinase/inhibitor complex, electron transport/electron transfer and lyase proteins.     

Recursive domains in proteins.

The domain is a fundamental unit of protein structure. Numerous studies have analyzed folding patterns in protein domains of known structure to gain insight into the underlying protein folding process. Are such patterns a haphazard assortment or are they similar to sentences in a language, which can be generated by an underlying grammar? Specifically, can a small number of intuitively sensible rules generate a large class of folds, including feasible new folds? In this paper, we explore the extent to which four simple rules can generate the known all‐β folds, using tools from graph theory. As a control, an exhaustive set of β‐sandwiches was tested and found to be largely incompatible with such a grammar. The existence of a protein grammar has potential implications for both the mechanism of folding and the evolution of domains.     

Dynamic proteins in bacteria.

The MinCDE system regulates the position of the division plane in rod-shaped bacteria. New results from Escherichia coli provide insight into how this operates by showing that MinE stimulates the ATPase activity of MinD.     

Ribosomal proteins in growing and starved Tetrahymena pyriformis. Starvation-induced phosphorylation of ribosomal proteins.

The complements of ribosomal proteins in growing and starved cells of Tetrahymena pyriformis strain GL were examined by two-dimensional gel electrophoresis. In growing cells, the 40-S ribosomal subunit contained 30 proteins, 4 of which migrated toward the anode at pH 8.6, while the 60-S ribosomal subunit contained 46 proteins, 9 of which migrated toward the anode at pH 8.6. When exponentially growing cells were transferred into a non-nutrient medium pronounced phosphorylation of a single 40-S ribosomal subunit protein, S6, was induced. The phosphorylation was very specific; more than 99.5% of the [32P]phosphate incorporated into ribosomal proteins was associated with S6. Phosphate was incorporated into S6 as O-phosphoserine and O-phosphothreonine. Two-dimensional gel electrophoresis indicated that the complement of proteins associated with the ribosomes isolated from starved cells differed from that of growing cells. Careful examination, however, suggested that except for the phosphorylation of certain ribosomal proteins in starved cells, the observed differences did not reflect starvation-induced changes in vivo, but most probably different levels of artifactual modifications (limited proteolysis) during the preparation of the ribosomes.     

Actin-binding proteins.

Much new information on the sequence, structure, and function of filament crosslinking, capping, and severing proteins is now known. Other significant findings include identification of a new abundant monomer-sequestering protein in platelets, and evidence that many actin-binding proteins interact with phosphoinositides and that this interaction may have metabolic consequences.     

Cobalt proteins.

In the form of vitamin B12, cobalt plays a number of crucial roles in many biological functions. However, recent studies have provided information on the biochemistry and bioinorganic chemistry of several proteins containing cobalt in a form other than that in the corrin ring of vitamin B12. To date, eight noncorrin-cobalt-containing enzymes (methionine aminopeptidase, prolidase, nitrile hydratase, glucose isomerase, methylmalonyl-CoA carboxytransferase, aldehyde decarbonylase, lysine-2,3-aminomutase, and bromoperoxidase) have been isolated and characterized. A cobalt transporter is involved in the metallocenter biosynthesis of the host cobalt-containing enzyme, nitrile hydratase. Understanding the differences between cobalt and nickel transporters might lead to drug development for gastritis and peptic ulceration.     

Adaptor-related proteins.

Two new adaptor-related protein complexes, AP-3 and AP-4, have recently been identified, and both have been implicated in protein sorting at the trans-Golgi network (TGN) and/or endosomes. In addition, two families of monomeric proteins with adaptor-related domains, the GGAs and the stoned B family, have also been identified and shown to act at the TGN and plasma membrane, respectively. Together with the two conventional adaptors, AP-1 and AP-2, these proteins may act to direct different types of cargo proteins to different post-Golgi membrane compartments.     

Cytotoxic proteins.

Cytotoxic proteins, which enter eukaryotic cells and catalytically inactivate protein synthesis, are being increasingly studied using a combination of molecular biology, cell biology and structural approaches. The creation of genetically engineered fusions with alternative cell-binding ligands paves the way for tailor-made, cell-type-specific killing agents.