Reviews & Analysis

A new fluorescent amino acid provides opportunities for a better understanding of electrostatics and dynamics in proteins and their role in protein function.

Bacterial RNA polymerase holoenzyme and open complex structures reveal how the σ subunit binds RNA polymerase and mediates the specific recognition of promoter DNA to facilitate transcription initiation.

A new study has demonstrated that the E. coli Hsp70, DnaK, can catalyze cis-trans isomerization of non-prolyl peptide bonds.

Housekeeping is not a humdrum process when it comes to protein quality control. Inside chaperone-protease machines, proteins are subject to dramatic life or death trials and must shape up rapidly to survive. Accumulation of aberrantly folded proteins is the basis of many diseases, so the outcome is vitally important to the cell.

A new 20-residue peptide represents the smallest example to date of cooperatively folded tertiary structure. This achievement provides a new tool for elucidating protein conformational preferences. The mini-protein should serve as a fruitful platform for protein design.

A lack of sequence similarity made it uncertain whether the four families of pseudouridine synthases arose by convergent or divergent evolution. The structures of three of these enzymes reveal that they are homologs, but a paucity of obvious catalytic residues in the active site reopens the question of a mechanism that seemed settled.

Proline in transmembrane helical segments is thought to play specific roles in membrane protein structure and function. Yet one of its primary contributions may occur even before the segment enters the membrane.

Two studies in this issue provide further insight into the structural continuum associated with the process of amyloidosis.

Proteins imported into mitochondria must be unfolded in order to pass through translocation pores present in the mitochondrial membranes. An article in this issue suggests that not only the heat shock protein 70 in the matrix, but also the electrical membrane potential across the inner membrane can actively unfold preproteins via a pulling mechanism.

The monomeric B₁₂-dependent ribonucleotide reductase from L. leichmannii has the central 10-stranded α/β-barrel found in all ribonucleotide reductases but incorporates two distinctive structural features, a novel cobalamin-binding fold and an insert forming part of a specificity control site that mimics the allosteric site found in the oligomeric di-iron dependent reductases.

Selective transport of cargo between membrane-bound organelles is vital for the well-being of cells. The crystal structure of a short peptide signal from the cytoplasmic tail of the mannose-6-phosphate receptor bound to the VHS domain of GGA proteins gives hints to how sorting works.

The discovery of two unexpected Ca²⁺-binding sites in the structure of a minimal catalytic domain of μ-calpain reveals a new mechanism underlying the Ca²⁺-dependent activation of calpains.

Φ-value analysis of the four-helix protein Im7 reveals that a folding intermediate with non-native structure rapidly forms en route to the native state, even though the protein topology is very simple. Energetic frustration, at least partially induced by functional constraints, appears to play a significant role.

The structure of the anthrax edema factor (EF) exotoxin reveals evidence of a new adenylate kinase mechanism and the first structure of an active calmodulin-dependent enzyme in complex with calmodulin (CaM). The CaM-free toxin opens to enfold CaM in a way that positions critical EF substrate-binding residues near the catalytic site.

The NSP3 protein from rotaviruses recognizes a unique sequence at the 3′ end of the rotaviral mRNA. By doing so, it promotes translation of viral proteins while repressing host protein synthesis. The structure of the NSP3 protein bound to a viral 3′ end sequence reveals how this occurs and suggests how it might be possible to design a new class of antiviral drugs.

Two new biophysical analyses of the folding behavior of model oligonucleosomal arrays have provided interesting new insights into how a histone mutation that mimics a chromatin remodeling activity and the incorporation of a histone variant into chromatin alter chromatin structure and function.

Protein import into chloroplasts is regulated by the binding and hydrolysis of GTP at two homologous GTPases, Toc34 and Toc159. The crystal structure of the Toc34 GTP-binding domain suggests that GTP-regulated dimerization of the Toc GTPase domains controls the targeting and translocation of preproteins at the chloroplast envelope.

The structure of a bacterial pheromone bound to its receptor sheds light on cell–cell signaling in bacteria.

A large kinetic barrier prevents spontaneous disassembly of SNARE complexes, complicating thermodynamic measurements and resulting in hysteresis. Nonetheless, this kinetic barrier is probably crucial for SNARE function.

The structures of peptide release factors raise new questions about their mechanism of action in protein synthesis.