Articles in 2016

EPR spectroscopy analyses elucidate how lipids affect the conformational dynamics of a multidrug secondary transporter, LmrP, and indicate a key role of the lipid headgroups in shaping the conformational-energy landscape of the transporter.

The pathogenesis of the nerve paralysis induced by botulinum neurotoxins begins with their specific and high-affinity binding to peripheral nerve terminals. The new crystal structure of the toxin bound to its glycosylated receptor, presented in this issue, represents a major step forward in the understanding of how botulinum neurotoxin type A1, the toxin used in human therapy and cosmetics, binds its protein receptor.

Contrary to conventional wisdom that molecular chaperones rely on hydrophobic interactions to bind a wide variety of client proteins in danger of misfolding, three recent studies reveal that the ATP-independent chaperone Spy exploits electrostatic interactions to bind its clients quickly, yet loosely enough to enable folding of the client while it is chaperone bound.

Solid-state NMR analyses reveal that the free backbone carbonyl groups associated with proline residues in the transmembrane helices play a key role in mediating rhodopsin activation.

The crystal structure of the putative exonuclease Exuperantia, required for Drosophila anterior patterning, reveals an EXO-SAM-like domain architecture that is catalytically inactive but mediates dimerization and RNA binding, which are essential for bicoid localization.

A new study reveals that 53BP1 influences high-fidelity homology-directed repair by showing that its depletion in the presence of increasing DNA-damage levels triggers a shift from RAD51-dependent gene conversion, an error-free process, to RAD52-mediated single-strand annealing, which is mutagenic.

Biochemical, structural and cell-based analyses reveal a chaperone-like function of glycyl-tRNA synthetase, which supports neddylation via direct interactions with NEDD8, E1 and E2.

Probing the synthetic lethal effect of FANCD2 deletion in BRCA2-deficient cells reveals independent roles of FANCD2 and BRCA2 in stabilizing stalled replication forks to maintain genome stability and promote cell survival.

BoNT/A1 invades motoneurons by binding to the neuronal receptor SV2. A combination of structural, biophysical and cellular analyses reveal that BoNT/A1 binding and uptake require glycosylation of SV2.

The histone methyltransferase DOT1L and the chromatin reader BRD4 together facilitate transcription of genes critical to the molecular pathogenesis of MLL leukemia.

Proteomic and genomic analysis of Polycomb group complexes in embryonic stem cells and neural progenitor cells identifies new PRC1 and PRC2 interaction partners and targets during neural lineage commitment.

Hydrogen/deuterium exchange mass spectrometry reveals that the antiapoptotic protein MCL-1 is inhibited by a covalent modification far from its functional site. This finding opens new avenues for cancer therapy, but it also highlights that much remains to be learned about the fundamental basis of allosteric regulation.

The noncoding RNA LINP1 acts as a scaffold that links Ku and DNA-PKcs and enables efficient DNA double-strand-break repair through nonhomologous end joining (NHEJ), thereby enhancing the resistance of triple-negative breast cancer cells to radiation and chemotherapies.

The importance of subtle gene regulation and epigenetics in determining complex human traits is increasingly being recognized. However, bridging the gaps between environmental, epigenetic and genetic influences and unraveling causal relationships remain a big challenge. A study now reports an example of epigenetic changes influenced by genetic factors that are involved in the regulation of lactase gene expression.

The first high-resolution views of group II intron maturases illuminate the architectural and functional roles of these multidomain proteins in splicing and DNA invasion. The maturases show striking structural and functional homology to a central protein involved in spliceosomal pre–messenger RNA splicing, thus reinforcing the idea that group II introns and the spliceosome descended from a common ancestor.

In a common yet effective analogy, a cell can be compared to a fortified city, in which lipid membranes form the defensive walls, and membrane proteins function as gates and checkpoints that control the transit of molecules and information across these walls. We evoke this concept on the cover of this special Focus on Membrane Proteins.

Wayne Hendrickson discusses the consortium efforts and developments in methodology that in recent years have allowed unprecedented advances in atomic-structure determination of membrane proteins.

This Perspective provides an overview of the major advances in recent years in the computational design and structure prediction of α-helical membrane proteins.