Proceedings of the Natural Academy of Sciences

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  • Respiration triggers heme transfer in mitochondria [Biochemistry]
    [Dec 2014]

    In exponentially growing yeast, the heme enzyme, cytochrome c peroxidase (Ccp1) is targeted to the mitochondrial intermembrane space. When the fermentable source (glucose) is depleted, cells switch to respiration and mitochondrial H2O2 levels rise. It has long been assumed that CCP activity detoxifies mitochondrial H2O2 because of the efficiency of...
    Categories: Journal Articles
  • Collagen fiber degradation by cathepsin K [Biochemistry]
    [Dec 2014]

    Cathepsin K is the major collagenolytic protease in bone that facilitates physiological as well as pathological bone degradation. Despite its key role in bone remodeling and for being a highly sought-after drug target for the treatment of osteoporosis, the mechanism of collagen fiber degradation by cathepsin K remained elusive. Here,...
    Categories: Journal Articles
  • Trajectories of the ribosome as a nanomachine [Biophysics and Computational Biology]
    [Dec 2014]

    A Brownian machine, a tiny device buffeted by the random motions of molecules in the environment, is capable of exploiting these thermal motions for many of the conformational changes in its work cycle. Such machines are now thought to be ubiquitous, with the ribosome, a molecular machine responsible for protein...
    Categories: Journal Articles
  • Distinct regulatory roles of PsbS and zeaxanthin [Biophysics and Computational Biology]
    [Dec 2014]

    The photosystem II (PSII) protein PsbS and the enzyme violaxanthin deepoxidase (VDE) are known to influence the dynamics of energy-dependent quenching (qE), the component of nonphotochemical quenching (NPQ) that allows plants to respond to fast fluctuations in light intensity. Although the absence of PsbS and VDE has been shown to...
    Categories: Journal Articles
  • NMR {Delta}{delta}NH/{Delta}T to design orally bioavailable peptides [Biophysics and Computational Biology]
    [Dec 2014]

    Enhancing the oral bioavailability of peptide drug leads is a major challenge in drug design. As such, methods to address this challenge are highly sought after by the pharmaceutical industry. Here, we propose a strategy to identify appropriate amides for N-methylation using temperature coefficients measured by NMR to identify exposed...
    Categories: Journal Articles
  • Electric fingerprint of voltage sensor domains [Biophysics and Computational Biology]
    [Dec 2014]

    A dynamic transmembrane voltage field has been suggested as an intrinsic element in voltage sensor (VS) domains. Here, the dynamic field contribution to the VS energetics was analyzed via electrostatic calculations applied to a number of atomistic structures made available recently. We find that the field is largely static along...
    Categories: Journal Articles
  • Chorismate mutase catalysis revisited [Biophysics and Computational Biology]
    [Dec 2014]

    For more than half a century, transition state theory has provided a useful framework for understanding the origins of enzyme catalysis. As proposed by Pauling, enzymes accelerate chemical reactions by binding transition states tighter than substrates, thereby lowering the activation energy compared with that of the corresponding uncatalyzed process. This...
    Categories: Journal Articles
  • GABA{rho} in cerebellar GFAP+ cells [Cell Biology]
    [Dec 2014]

    GABA-A receptors mediating synaptic or extrasynaptic transmission are molecularly and functionally distinct, and glial cells are known to express a plethora of GABA-A subunits. Here we demonstrate that GFAP+ cells of the granular layer of cerebellum express GABAρ subunits during early postnatal development, thereby conferring peculiar pharmacologic characteristics to GABA...
    Categories: Journal Articles
  • Mechanical-biochemical signaling remodels actin [Cell Biology]
    [Dec 2014]

    Cytoskeletal actin assemblies transmit mechanical stresses that molecular sensors transduce into biochemical signals to trigger cytoskeletal remodeling and other downstream events. How mechanical and biochemical signaling cooperate to orchestrate complex remodeling tasks has not been elucidated. Here, we studied remodeling of contractile actomyosin stress fibers. When fibers spontaneously fractured, they...
    Categories: Journal Articles
  • Substrate specificity of DHHC5 [Cell Biology]
    [Dec 2014]

    The cardiac phosphoprotein phospholemman (PLM) regulates the cardiac sodium pump, activating the pump when phosphorylated and inhibiting it when palmitoylated. Protein palmitoylation, the reversible attachment of a 16 carbon fatty acid to a cysteine thiol, is catalyzed by the Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferases. The cell surface palmitoyl acyltransferase DHHC5...
    Categories: Journal Articles
  • Body ownership causes illusory speaking [Computer Sciences]
    [Dec 2014]

    When we carry out an act, we typically attribute the action to ourselves, the sense of agency. Explanations for agency include conscious prior intention to act, followed by observation of the sensory consequences; brain activity that involves the feed-forward prediction of the consequences combined with rapid inverse motor prediction to...
    Categories: Journal Articles
  • Loss of host plants drives wild bee decline [Ecology]
    [Dec 2014]

    Evidence for declining populations of both wild and managed bees has raised concern about a potential global pollination crisis. Strategies to mitigate bee loss generally aim to enhance floral resources. However, we do not really know whether loss of preferred floral resources is the key driver of bee decline because...
    Categories: Journal Articles
  • Antimicrobial nanotherapeutics for H. pylori [Engineering]
    [Dec 2014]

    Helicobacter pylori infection is marked by a vast prevalence and strong association with various gastric diseases, including gastritis, peptic ulcers, and gastric cancer. Because of the rapid emergence of H. pylori strains resistant to existing antibiotics, current treatment regimens show a rapid decline of their eradication rates. Clearly, novel antibacterial...
    Categories: Journal Articles
  • Phytoplankton diversity and ocean phosphate uptake [Environmental Sciences]
    [Dec 2014]

    We have a limited understanding of the consequences of variations in microbial biodiversity on ocean ecosystem functioning and global biogeochemical cycles. A core process is macronutrient uptake by microorganisms, as the uptake of nutrients controls ocean CO2 fixation rates in many regions. Here, we ask whether variations in ocean phytoplankton...
    Categories: Journal Articles
  • Detecting tipping points in ecological networks [Environmental Sciences]
    [Dec 2014]

    Tipping points are crossed when small changes in external conditions cause abrupt unexpected responses in the current state of a system. In the case of ecological communities under stress, the risk of approaching a tipping point is unknown, but its stakes are high. Here, we test recently developed critical slowing-down...
    Categories: Journal Articles
  • Chicken domestication in China 10,000 years ago [Evolution]
    [Dec 2014]

    Chickens represent by far the most important poultry species, yet the number, locations, and timings of their domestication have remained controversial for more than a century. Here we report ancient mitochondrial DNA sequences from the earliest archaeological chicken bones from China, dating back to ∼10,000 B.P. The results clearly show...
    Categories: Journal Articles
  • Defective AlaRS editing causes cardiomyopathy [Genetics]
    [Dec 2014]

    Misfolded proteins are an emerging hallmark of cardiac diseases. Although some misfolded proteins, such as desmin, are associated with mutations in the genes encoding these disease-associated proteins, little is known regarding more general mechanisms that contribute to the generation of misfolded proteins in the heart. Reduced translational fidelity, caused by...
    Categories: Journal Articles
  • Structural characterization of the TCR-CD3 complex [Immunology and Inflammation]
    [Dec 2014]

    αβ T-cell receptor (TCR) activation plays a crucial role for T-cell function. However, the TCR itself does not possess signaling domains. Instead, the TCR is noncovalently coupled to a conserved multisubunit signaling apparatus, the CD3 complex, that comprises the CD3εγ, CD3εδ, and CD3ζζ dimers. How antigen ligation by the TCR...
    Categories: Journal Articles
  • c-Jun phosphorylation in macrophage phenotype [Immunology and Inflammation]
    [Dec 2014]

    The inflamed tumor microenvironment plays a critical role in tumorigenesis. However, the mechanisms through which immune cells, particularly macrophages, promote tumorigenesis have only been partially elucidated, and the full scope of signaling pathways supplying macrophages with protumorigenic phenotypes still remain largely unknown. Here we report that germ-line absence of c-Jun...
    Categories: Journal Articles
  • Actin regulates NLRC4 responses to Salmonella [Immunology and Inflammation]
    [Dec 2014]

    Salmonellosis is one of the leading causes of food poisoning worldwide. Controlling bacterial burden is essential to surviving infection. Nucleotide-binding oligomerization domain-like receptors (NLRs), such as NLRC4, induce inflammasome effector functions and play a crucial role in controlling Salmonella infection. Inflammasome-dependent production of IL-1β recruits additional immune cells to the...
    Categories: Journal Articles