Volume 22 Issue 6, June 2015

How do molecular interactions determine the period length of a circadian oscillator? In mammals, a disordered region of the BMAL1 transcription factor that is able to interact with activators or repressors seems to perform this function.

Sex-determining transcription factors recognize their genomic target sites through mechanisms of DNA base-and-shape readout in combination with cooperative binding. Murphy et al. reveal that for one such transcription factor, DMRT1, the DNA sequence-and-shape features of its binding sites determine whether it binds DNA as a dimer, trimer or tetramer; they also characterize protein-DNA contacts that affect gender phenotypes in flies and humans.

Ten years ago, the repulsive guidance molecules (RGMs), a family of three glycosylphosphatidylinositol–anchored glycoproteins, were identified as highly specific co-receptors of the bone morphogenetic proteins (BMPs). Newly reported crystal structures provide exciting insights into how RGM co-receptors may modulate BMP signaling.

DMRT transcription factors, key regulators of metazoan sexual development, use a unique DNA binding mode critical for male-to-female sex reversal in humans.

Single-molecule imaging reveals how stalled Escherichia coli RNA polymerase is displaced by the superfamily 2 DNA translocase (SF2) repair factor Mfd to permit transcription-coupled DNA repair.

Structural and functional analyses reveal how human repulsive-guidance-molecule glycoproteins activate bone morphogenic protein (BMP) signaling and physically link the latter to the neogenin pathway.

The crystal structure of the thermophilic 70S ribosome bound to the antimicrobial peptide Onc112 reveals that the peptide interacts with three adjacent functional sites in the ribosome.

Structural and biochemical studies reveal how the antimicrobial peptide Onc112 binds to bacterial ribosomes and show that Onc112 blocks and destabilizes the translation-initiation complex.

The mammalian circadian cycle is determined by sequential activation of clock target-gene expression by CLOCK–BMAL and subsequent repression by CRY. Biochemical and NMR data now show that Cry1 competes with coactivators for binding to the BMAL1 transcriptional-activation domain to regulate circadian cycling.

Evolution- and structure-guided mutagenesis allows elucidation of the solution NMR structure of the N-terminal domain of APOBEC3G. Mapping of HIV-1 Vif binding to the APOBEC3G NTD reveals an interaction interface distinct from those in other APOBEC3 proteins.

HDX-MS and cross-linking analyses by Hurley and colleagues reveal that the AAA+ ATPase Vps4 disassembles a substrate by global unfolding and translocation through its central pore, in a mechanism reminiscent of that of the unfoldase ClpX.

Aβ(1–42) is the most pathogenic amyloid-β species in Alzheimer's disease (AD). The solid-state NMR–based atomic model of an Aβ(1–42) fibril elucidates the mechanism of fibril formation and propagation in AD and other amyloid diseases.

Crystal structures of the Drosophila melanogaster dopamine transporter dDAT in complex with inhibitors reboxetine and nisoxetine shed light on the molecular basis of antidepressant selectivity and specificity.