Articles in 2010

The NoGo decay pathway involves the Dom34–Hbs1 complex and targets mRNAs that are stalled during translational elongation for cleavage. The structure of the Dom34–Hbs1 complex now reveals its structural similarity to release and elongation factor complexes. Upon binding Hbs1, Doom34 adopts a tRNA-like conformational change that suggests it would act to terminate translation.

Telomere shortening, senescence and aging are connected, but how the signal at shortening telomeres is transmitted to the cell more globally is unclear. H3 and H4 synthesis is now shown to be reduced as cell cultures age. This alters expression of Asf1, a histone chaperone, compromising the ability of aging cells to restore chromatin after replication and DNA. In this way localized effects at shortening telomeres can be propagated throughout the cell.

Tumor suppressor PALB2 is known to interact with BRCA1 and BRCA2, and to be required for the latter's localization to sites of DNA damage. Now PALB2 is shown to bind directly to DNA, to recombinase RAD51 and its accessory factor RAD51AP1. PALB2 also stimulates D loop formation by RAD51 in a synergistic manner with RAD51AP1.

Tumor suppressor PALB2 is known to interact with BRCA2 and promote homologous recombination in vivo. Now PALB2's activities have been studied, together with a BRCA2 chimeric protein, revealing that PALB2 binds D-loop structures, interacts directly with RAD51 and promotes strand invasion synergistically with BRCA2.

The 2009 pandemic flu influenza A H1N1 strain has caused great public health concern. Now the structure of H1N1 neuraminidase (NA) reveals that it lacks the characteristic additional cavity at its active site, known as the 150-cavity, found in all other known group 1 NAs.

Bacteriocins are toxins produced by bacteria to inhibit similar or related bacterial strains, and one such toxin, colicin E3, is known to target the ribosome by cleaving the 16S rRNA. The structure of the 70S ribosome in complex with the cytotoxic domain of colicin E3 now gives insight into the cleavage mechanism.

RecBCD is a bacterial complex that functions in repair of DNA breaks. The RecBC heterodimer has an ATPase motor (RecB) that translocates along ssDNA with a 3'->5' polarity. Now a second translocase activity is revealed in RecBC that moves the proteins along the opposite strand of a forked DNA at a similar rate.

Secretins are bacterial outer membrane proteins involved in different pathways for protein secretion or macromolecular complex assembly. Secretin can form a large oligomeric pore, whose opening needs to be carefully regulated. Now cryo-EM analysis of the Vibrio cholerae secretin GspD reveals a closed channel, with a constricted periplasmic vestibule, offering insight into the mechanism of GspD opening during protein secretion.

AZT is a nucleoside analog drug that inhibits HIV-1 reverse transcriptase (RT). The viral enzyme can acquire AZT resistance by mutations that enhance the rate of ATP-mediated excision of the incorporated AZT. Now structural work illustrates how the AZT resistance mutations create a high-affinity binding site for ATP and thus promote excision.

Ubr1 and Ubr2 are E3 ligases that target substrates by the N-end rule, and it is the UBR box that is needed for substrate recognition. The structures of the UBR boxes of human UBR1 and UBR2 show that they adopt a previously undescribed fold stabilized by zinc. One of the zinc-binding ligands is mutated in Johnson-Blizzard syndrome and leads to UBR box unfolding.

In the N-end rule pathway, the N-terminal residue of a protein is recognized by specific E3 ligases that promote its ubiquitination and proteasomal degradation. Now the structural basis for the recognition of N-terminal basic residues by the UBR box from yeast Ubr1 is solved. Together with functional analysis, the work reveals that the residue at position 2 of the substrate may influence the binding.

The C-terminal domain (CTD) of RNA polymerase II (Pol II) contains a number of repeats, phosphorylation of which influences RNA processing factor recruitment. Genome-wide CTD phosphorylation is now assessed and found not to be scaled to gene length. The kinases mediating these modifications are found not to alter Pol II distribution across a given gene uniformly, arguing that CTD phosphorylation is gene specific.

The exon junction complex (EJC) is found on spliced mRNAs and influences post-transcriptional regulation. It is now shown that in Drosophila melanogaster, the EJC is bound to some but not all spliced junctions, suggesting that its assembly by the splicing machinery is a regulated process.

The genome-wide occupancy profiles for yeast RNA polymerase II in different phosphorylated forms, as well as transcription factors, are presented. The resulting analysis captures a 5' transition in which initiation factors are replaced by a general set of elongation factors that form a productive complex, which disassembles in two steps at the 3' end of the gene.

The co-transcriptional processing of RNA depends on the precisely timed recruitment of different factors to the elongating transcript, which depends on the phosphorylation state of the C-terminal domain (CTD) of RNA polymerase II. Varani and coworkers show that two transcription termination factors, Rtt103 and Pcf1, bind specifically and cooperatively to Ser2-phosphorylated CTD. This provides a way to ensure that proper polyadenylation occurs only where Ser2 phosphorylation density is highest.

SpoT has a key role in the bacterial starvation response. Now the metazoan ortholog of SpoT, Mesh1, has been identified, and the structure reveals a conserved active site that can catalyze ppGpp hydrolysis. The Drosophila Mesh1 deletion mutant has impaired starvation resistance, and microarray analysis gives further insight into the starvation response.

“What do cells, genes, transposons, telomeres, RNA silencing and DNA recombination have in common? They were all discovered in plants.” This is how Rob Martienssen emphasizes the contributions of plant research. We asked plant scientists whether their field is getting adequate support and proper recognition and heard a resounding “no.”

The structure of Moxifloxacin, a quinolone antibacterial, in complex with Acinetobacter baumannii topoisomerase IV and DNA now shows how the drug stacks between base pairs at the DNA cleavage site. Moxifloxacin contacts the protein through a non-catalytic Mg²⁺, and the structure gives insight into the mode of inhibition and possible basis of drug resistance.

The structure of the small heat shock protein αB-crystallin, associated with multiple sclerosis and Alzheimer's disease, has eluded biologists for years. Small angle X-ray scattering and solid-state NMR reveal a curved dimer that modulates substrate interactions upon a change in pH.