Volume 23 Issue 6, June 2016

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 recent progress, successes, challenges and future opportunities in the application of solution NMR and solid-state NMR methods to study the structure, dynamics and function 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.

The use of nanodiscs is substantially fostering structural and functional studies of membrane protein. This Perspective summarizes the recent use of nanodiscs as an invaluable tool for the characterization of membrane proteins.

ABC transporters use ATP hydrolysis to translocate substrates across cell membranes. Kaspar Locher reviews the mechanistic diversity of ABC transporters, as has emerged from recent structural studies, and discusses future directions for investigation of ABC-transporter-catalyzed reactions.

Numerous recent crystal and cryo-EM structures have greatly advanced understanding of the functional mechanisms of neurotransmitter-gated ion channels. This Review discusses the structural basis of activation and desensitization mechanisms in glutamate and cysteine-loop receptors.

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.

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.

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 crystal structure of the GP1–GP2 complex of the prototypical arenavirus LCMV in prefusion form sheds light on the conformational changes that the arenavirus glycoprotein undergoes to cause fusion.

New data reveal that LINP1, a lncRNA overexpressed in triple-negative breast cancer, interacts with the Ku70–Ku80 complex and DNA-PKcs, thereby promoting NHEJ-mediated DNA double-strand-break repair.

Capsids from two herpesviruses (HSV-1 and PRV), imaged inside intact virions, are analyzed by cryo-EM. The maps allowed the construction of a complete model of subunit and domain organization, revealing extensive subunit contacts.

In vitro and in vivo analyses show that BRD4 has intrinsic acetyltransferase activity targeting histones H3 and H4, and BRD4 acetylation of H3 K122 results in histone eviction, nucleosome clearance and chromatin decompaction.

A 3.8-Å cryo-EM structure of a bacterial group IIA intron in complex with its intron-encoded protein reveals how the reverse transcriptase domain interacts with the mobile intron RNA as well as structural similarities with eukaryotic telomerase and spliceosomal components.

Crystal structures of the reverse transcriptase domains of two group II intron–encoded proteins reveal their similarity to the RT domain of splicing factor Prp8, thus suggesting a common ancestry shared by group II introns and the spliceosome.

Age-dependent epigenetic changes that are influenced by genetic factors contribute to lactase nonpersistence, which is linked to the inability of adult mammals to digest lactose.

Crystal structures, along with biochemistry data, capture the active form of the Dcp2 decapping enzyme in complex with Dcp1 and a peptide from Edc1, thus revealing the mechanism of activation by Dcp1 and Edc1 activators.

MSL1, a component of the Drosophila dosage compensation complex, genetically and biochemically interacts with CDK7, a subunit of the TFIIH transcription factor, thus revealing a complex interplay between MSL1 and the general transcriptional machinery.

A series of crystal structures and calculated free-energy landscapes of a Na⁺/Ca²⁺ exchanger explain how its alternating-access mechanism is controlled by the ion occupancy, thus leading to coupled antiport.

Identification of an allosteric mechanism disrupting the antiapoptotic BH3 binding activity of MCL-1 offers a new approach for targeting the apoptotic resistance of human cancers.

Analysis of changes in the EGFR interactome, ubiquitinome, phosphoproteome and proteome in response to EGF or TGF-α identifies RAB7 phosphorylation and RCP recruitment to EGFR as ligand-specific switches controlling receptor trafficking, signal duration and cellular responses.