Proceedings of the Natural Academy of Sciences

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  • Bacterial Na channel binds eukaryotic hNav blockers [Biochemistry]
    [Jun 2014]

    Voltage-gated sodium channels are important targets for the development of pharmaceutical drugs, because mutations in different human sodium channel isoforms have causal relationships with a range of neurological and cardiovascular diseases. In this study, functional electrophysiological studies show that the prokaryotic sodium channel from Magnetococcus marinus (NavMs) binds and is...
    Categories: Journal Articles
  • Ubiquitin Y59-E51 loop for K48-polyubiquitination [Biochemistry]
    [Jun 2014]

    Lysine 48 (K48)-polyubiquitination is the predominant mechanism for mediating selective protein degradation, but the underlying molecular basis of selecting ubiquitin (Ub) K48 for linkage-specific chain synthesis remains elusive. Here, we present biochemical, structural, and cell-based evidence demonstrating a pivotal role for the Ub Y59-E51 loop in supporting K48-polyubiquitination. This loop...
    Categories: Journal Articles
  • Real-time dynamics of LacY [Biochemistry]
    [Jun 2014]

    Galactoside/H+ symport across the cytoplasmic membrane of Escherichia coli is catalyzed by lactose permease (LacY), which uses an alternating access mechanism with opening and closing of deep cavities on the periplasmic and cytoplasmic sides. In this study, conformational changes in LacY initiated by galactoside binding were monitored in real time...
    Categories: Journal Articles
  • Characterization of bacterial cellulolytic LPMOs [Biochemistry]
    [Jun 2014]

    For decades, the enzymatic conversion of cellulose was thought to rely on the synergistic action of hydrolytic enzymes, but recent work has shown that lytic polysaccharide monooxygenases (LPMOs) are important contributors to this process. We describe the structural and functional characterization of two functionally coupled cellulose-active LPMOs belonging to auxiliary...
    Categories: Journal Articles
  • Photoactivatable fluorescent proteins [Biophysics and Computational Biology]
    [Jun 2014]

    Photoactivatable fluorescent proteins (PAFPs) have been widely used for superresolution imaging based on the switching and localization of single molecules. Several properties of PAFPs strongly influence the quality of the superresolution images. These properties include (i) the number of photons emitted per switching cycle, which affects the localization precision of...
    Categories: Journal Articles
  • Mirror-image conformation [Biophysics and Computational Biology]
    [Jun 2014]

    By using local (free-energy profiles along the amino acid sequence and 13Cα chemical shifts) and global (principal component) analyses to examine the molecular dynamics of protein-folding trajectories, generated with the coarse-grained united-residue force field, for the B domain of staphylococcal protein A, we are able to (i) provide the main...
    Categories: Journal Articles
  • Molecular-crowding effects on RNA folding kinetics [Biophysics and Computational Biology]
    [Jun 2014]

    The effects of “molecular crowding” on elementary biochemical processes due to high solute concentrations are poorly understood and yet clearly essential to the folding of nucleic acids and proteins into correct, native structures. The present work presents, to our knowledge, first results on the single-molecule kinetics of solute molecular crowding,...
    Categories: Journal Articles
  • Nanocrystal identification by EM [Biophysics and Computational Biology]
    [Jun 2014]

    The current practice for identifying crystal hits for X-ray crystallography relies on optical microscopy techniques that are limited to detecting crystals no smaller than 5 μm. Because of these limitations, nanometer-sized protein crystals cannot be distinguished from common amorphous precipitates, and therefore go unnoticed during screening. These crystals would be...
    Categories: Journal Articles
  • Protein-stabilizing mechanism of TMAO [Biophysics and Computational Biology]
    [Jun 2014]

    Although it is widely known that trimethylamine N-oxide (TMAO), an osmolyte used by nature, stabilizes the folded state of proteins, the underlying mechanism of action is not entirely understood. To gain further insight into this important biological phenomenon, we use the C≡N stretching vibration of an unnatural amino acid, p-cyano-phenylalanine,...
    Categories: Journal Articles
  • Cbf{beta} function in postnatal skeletogenesis [Cell Biology]
    [Jun 2014]

    The pathogenesis of cleidocranial dysplasia (CCD) as well as the specific role of core binding factor β (Cbfβ) and the Runt-related transcription factor (RUNX)/Cbfβ complex in postnatal skeletogenesis remain unclear. We demonstrate that Cbfβ ablation in osteoblast precursors, differentiating chondrocytes, osteoblasts, and odontoblasts via Osterix-Cre, results in severe craniofacial dysplasia,...
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  • Proteomaps of genome-wide abundance studies [Cell Biology]
    [Jun 2014]

    Proteomics techniques generate an avalanche of data and promise to satisfy biologists' long-held desire to measure absolute protein abundances on a genome-wide scale. However, can this knowledge be translated into a clearer picture of how cells invest their protein resources? This article aims to give a broad perspective on the...
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  • SREBF1 regulates mitophagy [Cell Biology]
    [Jun 2014]

    Genetic analysis of Parkinson disease (PD) has identified several genes whose mutation causes inherited parkinsonism, as well as risk loci for sporadic PD. PTEN-induced kinase 1 (PINK1) and parkin, linked to autosomal recessive PD, act in a common genetic pathway regulating the autophagic degradation of mitochondria, termed mitophagy. We undertook...
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  • Raft association determines PM localization [Cell Biology]
    [Jun 2014]

    The lipid raft hypothesis proposes lateral domains driven by preferential interactions between sterols, sphingolipids, and specific proteins as a central mechanism for the regulation of membrane structure and function; however, experimental limitations in defining raft composition and properties have prevented unequivocal demonstration of their functional relevance. Here, we establish a...
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  • Shear stress-dependent endocytosis in kidney cells [Cell Biology]
    [Jun 2014]

    The kidney has an extraordinary ability to maintain stable fractional solute and fluid reabsorption over a wide range of glomerular filtration rates (GFRs). Internalization of filtered low molecular weight proteins, vitamins, hormones, and other small molecules is mediated by the proximal tubule (PT) multiligand receptors megalin and cubilin. Changes in...
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  • Bcl-2 family indirectly regulates autophagy [Cell Biology]
    [Jun 2014]

    Antiapoptotic B-cell lymphoma 2 (Bcl-2) family members such as Bcl-2, myeloid cell leukemia 1 (Mcl-1), and B-cell lymphoma-X large (Bcl-xL) are proposed to inhibit autophagy by directly binding to the BH3 domain of Beclin 1/Atg6. However, these Bcl-2 family proteins also block the proapoptotic activity of Bcl-2–associated X (Bax) and...
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  • Structure of intein branched intermediate [Chemistry]
    [Jun 2014]

    Inteins are autoprocessing domains that cut themselves out of host proteins in a traceless manner. This process, known as protein splicing, involves multiple chemical steps that must be coordinated to ensure fidelity in the process. The committed step in splicing involves attack of a conserved Asn side-chain amide on the...
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  • Removing T-cell epitopes with protein design [Computer Sciences]
    [Jun 2014]

    Immune responses can make protein therapeutics ineffective or even dangerous. We describe a general computational protein design method for reducing immunogenicity by eliminating known and predicted T-cell epitopes and maximizing the content of human peptide sequences without disrupting protein structure and function. We show that the method recapitulates previous experimental...
    Categories: Journal Articles
  • Simple generation of all retinal cells from hiPSC [Developmental Biology]
    [Jun 2014]

    Progress in retinal-cell therapy derived from human pluripotent stem cells currently faces technical challenges that require the development of easy and standardized protocols. Here, we developed a simple retinal differentiation method, based on confluent human induced pluripotent stem cells (hiPSC), bypassing embryoid body formation and the use of exogenous molecules,...
    Categories: Journal Articles
  • Earth's oldest trace fossil reevaluated [Earth, Atmospheric, and Planetary Sciences]
    [Jun 2014]

    Microtextures in metavolcanic pillow lavas from the Barberton greenstone belt of South Africa have been argued to represent Earth’s oldest trace fossil, preserving evidence for microbial life in the Paleoarchean subseafloor. In this study we present new in situ U–Pb age, metamorphic, and morphological data on these titanite microtextures from...
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  • Chaos-order transition in foraging of ants [Ecology]
    [Jun 2014]

    The study of the foraging behavior of group animals (especially ants) is of practical ecological importance, but it also contributes to the development of widely applicable optimization problem-solving techniques. Biologists have discovered that single ants exhibit low-dimensional deterministic-chaotic activities. However, the influences of the nest, ants’ physical abilities, and ants’...
    Categories: Journal Articles