Articles in 2008

Rad51 is an essential protein with a central role in homologous recombination. An N-end rule degron Rad51 is now used in DT-40 cells to show that Rad51 is not required for DNA synthesis, but it is necessary to resolve RPA-bound DNA structures during G2.

SRp38, unlike other SR proteins, functions as a general splicing repressor when it is dephosphorylated. When phosphorylated it functions as a sequence-specific splicing activator and also affects the selection of mutually exclusive exons in the GluR-B pre-mRNA. Thus, SRp38 is a previously uncharacterized kind of splicing factor that can switch from a repressor to an activator and regulator of alternative splicing.

Viral fusion proteins are required for the fusion of viral and host membranes for all enveloped viruses. The structure of the Baculovirus postfusion form of glycoprotein gp64, a class III fusion protein, explains its ability to fuse with many different cell types, and structural comparisons suggest that all three classes of fusion proteins may be more closely related than previously thought.

Caspases are cysteine proteases that have a central role in triggering apoptosis; thus, it is essential to tightly control their activity. Now a caspase inhibitor has been identified in Caenorhabditis elegans: CSP-3 is a caspase homolog that associates with the CED-3 zymogen, inhibiting its autoactivation.

Mutation of Cid14, a key enzyme in the TRAMP RNA surveillance pathway, has previously been shown to decrease small interfering RNA production in Schizosaccharomyces pombe. Analysis of Argonaute-associated proteins now indicates that, in the absence of Cid14, RNAs usually processed by TRAMP now enter the small interfering RNA pathway, suggesting that the RNA surveillance pathway prevents abundant RNAs from entering the RNA interference pathway.

Certain bacterial enzymes are packaged within protein chambers that provide a confined environment for their reactions to take place. Ban and colleagues now identify a family of proteins that form nanocompartments, similar to bacterial microcompartments such as the carboxysome, and show that the enzymes within are anchored by their C-terminal extensions to binding sites on the inner surface of the chamber.

MicroRNAs are processed by Drosha, and previous data had suggested that this occurred soon after transcription. Following Drosha recruitment and using nuclear run-on technology, data now indicate that miRNAs both within and outside of introns are processed co-transcriptionally and that exonucleases enter the fray to aid processing before splicing, implying that Drosha cleavage influences the maturation of the pre-mRNAs in which miRNAs reside.

Formation of β-2 microglobulin (β2m) amyloid fibrils is associated with dialysis-related amyloidosis. β2m pre-amyloid formation occurs in a Cu²⁺-dependent manner in vitro. Structural studies reveal that structural changes away from the Cu²⁺ binding site create conditions that promote β2m oligomerization leading to amyloidogenesis.

The Est3 telomerase subunit has a critical, but still uncharacterized regulatory role in yeast telomere maintenance. An OB-fold is now predicted for Candida albicans Est3 protein, and residues important for its association with the telomerase complex are identified.

The Est3 telomerase subunit has a critical, but still uncharacterized regulatory role in yeast telomere maintenance. An OB-fold is now predicted for Saccharomyces cerevisiae Est3 protein, and residues important for its association with the telomerase complex are identified.

In pregnancy-associated malaria, parasite-infected erythrocytes express the protein VAR2CSA on their surface and bind to chondroitin sulfate A in the placenta, with severe effects to the mother and the fetus. Now the crystal structure of a domain of VAR2CSA in complex with chondroitin sulfate A is reported and, together with functional studies, sheds insight into this interaction.

Group A trichothiodystrophy is caused by mutations in the p8 subunit of the TFIIH complex, involved in transcription and nucleotide-excision repair. Now the structure of the yeast ortholog of p8 in complex with a fragment of the yeast ortholog of p52 shows how p8 stabilizes p52 and thus the whole TFIIH complex.

The ribosomal GTPase, LepA or EF4, can promote back-translocation of tRNAs, thus reversing translocation. The cryo-EM structure of the ribosome with EF4 now suggests how such back-translocation can be allowed to occur and reveals that the tRNA is in an intermediate state that deviates from its canonical position.

The architecture of heterochromatin is maintained by HP1, which is known to interact with the p150 subunit from the histone chaperone complex CAF-1. This interaction is now shown to be important for the replication of pericentric heterochromatin regions during late S phase in mouse cells, a role that is independent of CAF-1's histone-deposition activity.

PPARγ is a nuclear receptor that regulates metabolic homeostasis and whose physiological ligands are nitrated and oxidized fatty acids. The crystal structures of the ligand binding domain of PPARγ in complex with several oxidized fatty acids are now described, showing differences with synthetic agonists that may have physiological relevance.

The structure of yeast Vps75, a histone chaperone that associates with the Rtt109 histone acetyltransferase, is presented and compared to Nap1, which interacts with the same histone acetyltransferase.

Vps75 is a histone chaperone that associates with the Rtt109 acteyltransferase. The structure of Vps75 and further biochemical analysis suggest how Vps75 functions to alter histone H3K9 acetylation during S phase, and suggest a model for how it activates the histone acetyltransferase.

The interaction between the signal-recognition particle (SRP) and its receptor (SR) is catalyzed by the RNA component of SRP, but the mechanism is not clear. Now, kinetics and NMR studies reveal an inhibitory role of the N-terminal helices of both proteins, suggesting that the RNA facilitates formation of the SRP–SR complex by promoting conformational changes of these helices.

The Nrd1 pathway is involved in turnover of cryptic untranslated transcripts. The recruitment of Nrd1 is now shown to be dependent upon the phosphorylation status of the RNA polymerase II C-terminal domain and the distance from the 5′ end of the gene, suggesting a model where this distance determines the termination pathway used.

Type II chaperonins, such as CCT, and Hsp70 class chaperones, such as Hsc70, have crucial roles in protein folding and share some substrate overlap. Structural data now indicate that a complex forms between the β subunit of CCT and Hsc70, suggesting a coordinated hand-off mechanism for substrate interactions.