Volume 9 Issue 3, March 2013

Physiologically relevant ligands for mammalian odorant receptors have been elusive. A mouse odorant receptor–based bioassay has now been used to guide purification and identification of a natural ligand that mediates attraction of female mice to male urine.

PUMA is a BCL-2 family protein that transmits stress signals to promote apoptosis. Upon DNA damage, a unique binding determinant within PUMA triggers partial unfolding of BCL-X_L, resulting in the release of sequestered p53 and commitment to p53-dependent cell death.

Control of protein self-assembly and disassembly, which is central to metabolism and engineering applications, remains challenging. Here, a perspicacious redesign of interfaces in the multisubunit ferritin protein cage provides single, modifiable subunits that assemble with Cu²⁺ templating and give insights into the cage assembly code.

Beyond their canonical functions of charging tRNAs with amino acids for protein translation, tRNA synthetases have numerous nontranslational roles that regulate signaling, immunity and development.

Ubiquitin-conjugating (E2) enzymes contain a conserved asparagine that has been proposed to stabilize an oxyanion intermediate. Structural and biochemical studies of Ubc13 suggest that this residue has a structural role in stabilizing the E2 active site.

Heterologous expression of the two components of enterococcal cytolysin with a lanthionine synthetase enables the structural determination of this antimicrobial and hemolytic pair, revealing unexpected stereochemistry in one of the lanthionine bridges that is driven by peptide sequence.

A natural aliphatic alcohol ligand of the mouse orphan odorant receptor Olfr288 from the male preputial gland is regulated by testosterone and affects attractiveness to female mice.

π-stacking interactions unique between residues of PUMA and Bcl-xL, which lead to the unfolding of Bcl-xL via an allosteric mechanism, are required to disrupt p53–Bcl-xL interaction and induce apoptosis. This is the first example of regulated protein unfolding for signal transmission.

A new protein engineering approach inserts metal-coordination motifs to stabilize natural protein interfaces while other favorable contacts are removed, yielding metal-inducible protein-protein interactions that have allowed the study of a self-assembling protein cage and the chemical labeling of its interior.

Structural analyses reveal that CopA and CupA share a binuclear Cu(I) ion binding motif and that copper is trafficked from a low-affinity site on CupA to a high-affinity site in CopA, making CupA the first membrane-bound copper chaperone important in copper resistance.

Methylation of lysine residues regulates chromatin function in part by recruiting readers to these marks. UNC1215, a selective antagonist of the methyllysine reader L3MBTL3 with a polyvalent mode of interaction, reveals BCLAF1 as a methyllysine-dependent interaction partner for L3MBTL3.