|Nature Structural aamp; Molecular Biology - Issue - nature.com science feeds|
The Seventh International Conference on the Hsp90 Chaperone Machine took place in October 2014, in Seeon, Germany. The program highlighted recent findings in a variety of areas, including structures of heat-shock protein 90 (Hsp90)–client protein complexes, coordination of Hsp90 with cochaperones, new cellular and physiological roles for Hsp90 and therapeutic targeting of the Hsp90 ensemble for the treatment of disease and prevention of infection.
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.
Integrinα-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.
|Nature Structural aamp; Molecular Biology - AOP - nature.com science feeds|
Bacterial LPS O-antigen is synthesized with a narrow size range by polymerase WbdA and terminating protein WbdD. An extended coiled-coil domain in WbdD determines the length of the synthesized O-chain, acting as a molecular ruler.
Gronemeyer and colleagues identify naturally occurring double-stranded RNAs arising from sense-antisense transcript pairs and demonstrate that one of these RNAs, nds-2a, interacts with mitotic protein complexes and is required for cellular mitosis.
5-Formylcytosine (5fC) is implicated in active DNA demethylation and has been proposed to act as an epigenetic signal. Balasubramanian and colleagues now report that this base modification imparts a unique, previously undescribed conformation to DNA.
Cytoplasmic dynein has multiple ATPase subunits, with AAA1 as the primary ATPase. Single-molecule and biochemical approaches reveal that AAA3 ATPase has a role in switching dynein between cargo-transport and microtubule-anchoring modes.
Bacterial ABC importer GlnPQ has two fused substrate-binding domains (SBDs). Single-molecule FRET is now used to probe the conformational dynamics of the SBDs, which are shown to directly influence transport rates.
Different catalytic steps of endonuclease I-DmoI are captured crystallographically to allow direct observation of the generation of a DNA double-strand break. A third metal ion enters the active site and has a key role in hydrolysis.
Myo1c is a monomeric, unconventional myosin that can sense mechanical force in the cell. The structure of Myo1c's entire tail and neck domains in complex with apocalmodulin reveals a new mode of calmodulin interaction.
All RAF kinase domain structures reported to date have adopted a dimer configuration. Marc Therrien, Frank Sicheri and colleagues now report a crystal structure of the BRAF monomeric 'off' state, providing insight into its catalytic activation.