Volume 15 Issue 9, September 2008

Peroxisome proliferator–activated receptor-γ (PPARγ) is a ligand-regulated transcription factor with crucial roles in carbohydrate and lipid metabolism and adipogenesis, but the structural details of the binding and activation by endogenous ligands are not known. Two recent studies reveal how oxidized and nitrated fatty acids uniquely bind and activate PPARγ.

The crystal structure of the CSA-binding Duffy-binding-like domain DBL3x of the VAR2CSA-encoded PfEMP1 adhesin has been solved in the free state and complexed with CSA oligosaccharides, shedding light on the major host-parasite interaction in pregnancy-associated malaria.

Bacteria sequester key metabolic steps into polyhedral protein compartments. A newly discovered nanocompartment reveals what it takes for its cargo protein to become encapsulated within a protein shell.

Cohesin is a large ring-shaped protein complex that mediates cohesion between sister chromatids. New experiments show that the sister chromatids of a minichromosome are entrapped by monomeric cohesin rings, thus excluding the possibility that sister chromatid cohesion is mediated by nontopological interactions between cohesin complexes.

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.

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 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.

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.

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.

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.

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 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.

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 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.

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 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.