Volume 21 Issue 12, December 2014

cIAP1 undergoes a dramatic conformational change during activation that is now shown to be due to the dynamic and metastable nature of the closed form of the enzyme. The discovery of such a striking mechanism for functional control was enabled by state-of-the-art enzymological and biophysical methods.

Two studies provide insights into the distinct strategies used by prokaryotes and eukaryotes to pause translation in order to facilitate cotranslational targeting of membrane proteins to the translocon.

Two complementary papers demonstrate that the homologous type II transmembrane proteins LAP1 and LULL1 adopt nucleotide-free AAA+ ATPase folds and donate arginine fingers to complete the active sites of Torsin AAA+ ATPases. Activated Torsin complexes appear to function in nuclear and endoplasmic reticulum membrane-remodeling processes, including a nuclear vesiculation pathway that carries large cellular and viral cargoes from the nucleus into the cytoplasm.

Reconstitution of a 15-subunit functional human Mediator complex establishes direct physical and functional interactions of key MED subunits with both Pol II and TFIID to support transcriptional activation and identifies subunits critical for module association and assembly.

The BBSome is required for formation of primary cilia, sensory organelles whose dysfunction is linked to genetic disorders. Lorentzen and colleagues offer insight into BBSome membrane recruitment, providing a molecular rationale for common disease mutations.

Cryo-EM structures of the co-translational chaperone RAC in association with the ribosome suggest that RAC regulates protein translation by mechanically coupling cotranslational folding with the peptide-elongation cycle.

BRD4, a key target of the clinically relevant BET inhibitor JQ1, thought to function by releasing Pol II from promoter-proximal pausing, is shown to promote Pol II elongation by acting as a histone chaperone.

Peptide hydrocarbon stapling is used to generate protease-resistant HIV-1 MPER antigens that mimic the conformation of viral epitopes and that are recognized by two different broadly neutralizing antibodies to HIV.

Proapoptotic signals trigger the transition of cIAP1 from an autoinhibited monomeric form to an activated dimer. NMR and time-resolved SAXS analyses reveal the conformational dynamics of the cIAP1 monomer that facilitates rapid and irreversible activation.

Cryo-EM analyses of coronin in complex with F-actin in its ADP-bound or ADP–BeFx–bound state and fitting of atomic models explain the nucleotide-dependent effects of coronin on cofilin-assisted remodeling of F-actin.

Work in Caenorhabditis elegans identifies a substrate for CED-3 caspase during apoptosis, CNT-1. The cleavage product of CNT-1 localizes to the plasma membrane and blocks the activation of AKT by PIP3, suppressing AKT's prosurvival effects.

Integrin α-β heterodimers recognize ligands with RGD peptide motifs, but how they differentiate between the numerous RGD-containing proteins is unknown. Here, Springer and colleagues elucidate the structural basis for ligand binding specificity of the integrin β subunit.

A new crystal structure of BtuCD, a bacterial ABC transporter that uses ATP hydrolysis to drive vitamin B12 uptake, bound to an AMP-PNP nucleotide, completes the structural elucidation of intermediates in the transport cycle and reveals how ATP accelerates transport.

Analyses of yeast codon usage and ribosome profiling data reveal a nonoptimal codon cluster in the mRNAs of ER-targeted proteins, downstream of the SRP-binding site, that would slow down translation to promote SRP interaction.