Volume 19 Issue 5, May 2012

Methylated histone H3 Lys9 is a hallmark of heterochromatin, and directs DNA methylation via a complex containing heterochromatin protein 1 (HP1) and a DNA methyltransferase. Genetic and biochemical studies in Neurospora now identify a distinct HP1 complex containing a histone deacetylase that is required for silencing independently of DNA methylation, suggesting that distinct HP1 complexes function in parallel to assemble silent heterochromatin.

SUV39H1 is a histone methyltransferase responsible for the repressive H3K9me3 mark. New data indicate that SUV39H1, via p21, is a target of p53 repression, leading to decreased H3K9me3 levels at p53 promoters and facilitating p53 activation of its target genes.

The membrane-embedded c-ring allows the passage of protons to power the synthesis of ATP by the FoF1 ATPase. Previous structural data have shown the proton acceptor-donor sites in a closed, ion-locked conformation. Structural and computational data now reveal the open conformation of the yeast mitochondrial c₁₀ ring.

Dynein is a molecular motor involved in many cellular functions. The motor domain of dynein contains six AAA+ domains forming a ring that interacts with the motile linker domain. The structure of yeast dynein motor domain crystallized without nucleotides is now presented at 3.3-Å resolution and shows the specific contacts between linker and ring, with nucleotide interactions at the different AAA+ domains revealed by soaking experiments.

The nonsense-mediated mRNA decay (NMD) pathway is triggered upon assembly of the UPF surveillance complex near an exon junction complex (EJC). Cryo-EM studies have revealed the geometry of this transient assembly between the UPF complex and the EJC, which demonstrates how the UPF1 subunit elicits its RNA helicase activity toward the 3A end of the mRNA.

Bacterial secretion systems are key to pathogenesis, as they secrete the many virulence factors needed for host colonization. Bioinformatic and functional analyses have identified a transport and assembly module (TAM) in proteobacteria that may be necessary for biogenesis of the autotransporter family of virulence factors.

The AAA+ protein p97 and its UBA-UBX cofactors are thought to promote degradation by separating ubiquitinated proteins from membranes or protein complexes. UBA-UBX proteins can interact with cullin-RING ubiquitin ligases, and UBXD7 is now seen to specifically bind NEDD8 on active, neddylated cullins, promoting degradation of a Cul3 substrate.

The association of Argonaute (Ago) proteins with endomembranes is thought to be important for their function. New analyses now demonstrate that a transmembrane form of human prion protein binds Ago through GW-motif-containing octarepeat domains and promotes the accumulation of miRISC effector complexes, thereby mediating effective repression of miRNA targets.

Mechanistic studies of active exchangers suggest that substrate binding in active exchangers is antagonistic, and coupling is maintained by preventing shuttling of the empty transporter. However, isothermal titration calorimetry and free energy calculations now show that substrate binding of H⁺ and Cl⁻ to the prokaryotic CLC-ec1 exchanger is synergistic and occurs simultaneously.

Liver receptor homolog 1 (LHR-1) is a nuclear receptor involved in development, lipid homeostasis and metabolism. The crystal structures of the LHR-1 ligand-binding domain in its apo state and in complex with the phospholipid DLPC are now presented. The data, along with biophysical and functional analyses, reveal the highly dynamic nature of the apo receptor and show how DLPC binding affects co-regulator selectivity.

Bacterial DNA gyrase uses the energy from ATP to introduce negative supercoils into DNA via formation of a chiral wrap intermediate. Now DNA rotation and contraction are simultaneously visualized using a single-molecule setup. The data reveal multiple steps, including a dominant non-chiral intermediate step.

Heparan sulfate can promote formation of amyloid fibrils by different proteins. The early steps and kinetics of this process are now studied in detail, using a stopped-flow setup and the protein mAcP. The data and analysis reveal two steps, binding of mAcP to heparan sulfate and conversion to a misfolded state, followed by aggregation of the heparan sulfate–bound proteins.

Group II introns, which are self-splicing catalytic RNAs, catalyze splicing in two distinct steps. The crystal structure of a group II intron in the pre-catalytic state directly preceding the first splicing step reveals a sharp kink in the backbone that presents the scissile phosphate of the splice site to the active site.