Building on previous work (Froelich et al., 2014), we present the X-ray crystal structure of an active MCM hexamer, which suggests a mechanism for MCM regulation and demonstrates a key interaction between the major domains.
Rigorous assays of membrane fusion show that a distinct tethering step is required for lumenal compartment mixing in a manner that extends beyond simply increasing the amount of total trans-SNARE complex.
Developing long bones contain distinct mesenchymal stem-cell populations derived from mesoderm and neural crest, which have specialized functions in skeleton formation and the establishment of the hematopoietic stem-cell niche, respectively.
Ligand binding to the ectodomain of the insulin-like growth factor receptor destabilises an autoinhibitory inter-subunit interaction, which allows the transmembrane domains to associate and the intracellular regions to autophosphorylate.
Whole-genome in silico screening for stop codon contexts that produce elevated translational readthrough and peroxisome targeting reveals that in mammals, the amount of lactate dehydrogenase in the peroxisome is controlled by translational readthrough.
A transport mechanism is uncovered in the major drug-efflux system in E. coli involving two remote alternating-access conformational cycles, which could provide the basis for the development of allosteric inhibitors against multidrug resistance.
Transcribed promoters are highly susceptible to mutation by cytidine deaminases, implicating stable exposure of single stranded DNA structures, rather than cofactors, in localising mutation during tumourigenesis and antibody maturation.
Eukaryotic translation elongation factor 1A1 controls the process of heat shock response, from transcriptional activation of the HSP70 gene, to HSP70 mRNA stabilization, nuclear export, and translation.
The SCHENGEN3 protein is needed for the progression of isolated microdomains into a continuous band, which is necessary for the establishment of the major extracellular diffusion barrier in plant roots: the Casparian strip.
The pattern of past Ebola outbreaks is indicative of an effective reproductive ratio of less than 1, which can lead to the generation of a range of outbreak sizes consistent with the scale of the ongoing epidemic.
Measuring HIV-1 DNA levels at the time of stopping antiretroviral therapy (when initiated during primary infection) predicts clinical progression and the time taken for plasma viraemia to become detectable.
Cryo-electron microscopy reconstructions of two microtubule-bound transport kinesins at 7 Å resolution reveal how microtubule track binding stimulates ADP release, primes the active site for ATP binding and enables force generation.
Transcription profiling of activated cells using Phospho-Trap, a new method for identifying activated cells, reveals a critical role for mTOR signaling in red blood cell development and the pathogenesis of anemia
The theory of Buffered Qualitative Stability uses the importance of biological robustness to explain many features of gene regulatory networks in a wide range of organisms, and has implications for diverse biological phenomena including the ability of bacteria and cancer cells to ‘loosen’ their robustness and hence evade treatment.
Structure-function analyses reveal the mechanistic underpinnings of inside-out transmembrane signaling that controls periplasmic proteolysis, and thereby biofilm formation, in bacteria and may be relevant in the context of other signaling proteins with similar control elements.