Volume 22 Issue 2, February 2015

Little is currently known about the molecular determinants of energy barriers along enzyme catalytic pathways. Kern and co-workers have studied this question in adenylate kinase (Adk) and now reveal that a single Mg²⁺ ion can accelerate two distinct steps, thus uncovering an unexpected dual role for this ubiquitous cofactor.

The structural rules governing the curving folds of solenoid proteins, as distilled down to the level of the underlying sequence repeats, provide designers with the tools to reliably fashion new variants with tunable geometries. Bespoke leucine-rich repeat (LRR) scaffolds, as recognition proteins, can now be tailored to better fit their targets.

The ryanodine receptor (RyR), an ion channel regulating intracellular calcium release in excitable cells, has been challenging for structural analysis because of its colossal proportions compared to most other ion channels. Three independent groups have now used recent technological advancements in single-particle cryo-EM to make giant strides in solving the structure of this elusive protein complex.

Toll-like receptors (TLRs) have key roles in innate immunity. Here, Shimizu and colleagues report crystal structures of TLR8 in complex with single-stranded RNA that reveal the molecular basis for recognition of a natural ligand.

Oxidative stress induces a number of cellular responses. Silva et al. uncover a peroxide-mediated K63-linked polyubiquitination pathway, and identify its targets and regulators.

Structural, computation and kinetics approaches reveal the energy landscape of catalysis by adenylate kinase and show that the cofactor Mg²⁺ activates two distinct molecular events in the reaction cycle: phosphoryl transfer and lid opening.

The γ-tubulin ring complex (γTuRC) nucleates microtubules in the cell. The functional, closed state of yeast γTuRC is now visualized, and its microtubule-nucleating activity is found to be species specific.

Aquarius is an RNA helicase associated with spliceosomes. Lührmann, Pena and colleagues now provide structural insights into how Aquarius is recruited to the spliceosome, revealing a new spliceosomal building block that aids in Aquarius positioning.

Proteins with charged amino acid residues encounter an electric force as they transit through membranes holding membrane potential. Von Heijne and colleagues measure this force to assess how membrane electrostatics contributes to translocation dynamics.

CtIP helps maintain genomic stability by promoting DNA double-strand-break repair. Structural and biophysical analyses now show that the N terminus of human CtIP forms a tetrameric structure that is required for resection of broken DNA ends to permit their repair by homologous recombination.

Structural, biophysical and genetic analyses reveal that Schizosaccharomyces pombe Ctp1 forms a flexible tetramer with multivalent DNA-binding and bridging activities that contribute to Ctp1's role in repair of DNA double-strand breaks.

Leucine-rich repeats (LRRs) can form horseshoe-like structures with different curvatures in nature. A computational approach now allows the design of 12 new LRR proteins with precise curvatures, using defined building blocks and junction modules.