Proceedings of the Natural Academy of Sciences

Proceedings of the National Academy of Sciences RSS feed -- current issue
  • Circadian rhythm of Prx hyperoxidation in RBCs [Biochemistry]
    [Aug 2014]

    The catalytic cysteine of the typical 2-Cys Prx subfamily of peroxiredoxins is occasionally hyperoxidized to cysteine sulfinic acid during the peroxidase catalytic cycle. Sulfinic Prx (Prx–SO2H) is reduced back to the active form of the enzyme by sulfiredoxin. The abundance of Prx–SO2H was recently shown to oscillate with a period...
    Categories: Journal Articles
  • Order-disorder in hemagglutinin rearrangement [Biophysics and Computational Biology]
    [Aug 2014]

    Influenza hemagglutinin (HA), a homotrimeric glycoprotein crucial for membrane fusion, undergoes a large-scale structural rearrangement during viral invasion. X-ray crystallography has shown that the pre- and postfusion configurations of HA2, the membrane-fusion subunit of HA, have disparate secondary, tertiary, and quaternary structures, where some regions are displaced by more than...
    Categories: Journal Articles
  • Ligand binding and allostery in the KIX system [Biophysics and Computational Biology]
    [Aug 2014]

    The kinase-inducible domain interacting (KIX) domain of CREB binding protein binds to multiple intrinsically disordered transcription factors in vivo at two distinct sites on its surface. Several reports have been made of allosteric communication between these two sites in this well-characterized model system. In this work, we have performed fluorescence...
    Categories: Journal Articles
  • Defining allosteric effects in KIX complexes [Biophysics and Computational Biology]
    [Aug 2014]

    Allosteric binding events play a critical role in the formation and stability of transcriptional activator–coactivator complexes, perhaps in part due to the often intrinsically disordered nature of one or more of the constituent partners. The kinase-inducible domain interacting (KIX) domain of the master coactivator CREB binding protein/p300 is a conformationally...
    Categories: Journal Articles
  • Allosteric regulation in KIX [Biophysics and Computational Biology]
    [Aug 2014]

    The kinase-inducible domain interacting (KIX) domain of the CREB binding protein (CBP) is capable of simultaneously binding two intrinsically disordered transcription factors, such as the mixed-lineage leukemia (MLL) and c-Myb peptides, at isolated interaction sites. In vitro, the affinity for binding c-Myb is approximately doubled when KIX is in complex...
    Categories: Journal Articles
  • Cooperative ribosomal dynamics during translation [Biophysics and Computational Biology]
    [Aug 2014]

    One of the most challenging unanswered questions regarding the structural biology of biomolecular machines such as the two-subunit ribosome is whether and how these machines coordinate seemingly independent and random conformational fluctuations to maximize and regulate their functional efficiencies. To address this question, we have used ribosome mutagenesis or a...
    Categories: Journal Articles
  • Protein unfolded state energetics [Biophysics and Computational Biology]
    [Aug 2014]

    Unfolded and partially unfolded proteins participate in a wide range of biological processes from pathological aggregation to the regulation of normal cellular activity. Unfolded states can be populated under strongly denaturing conditions, but the ensemble which is relevant for folding, stability, and aggregation is that populated under physiological conditions. Characterization...
    Categories: Journal Articles
  • Prion-like proteins suppress huntingtin toxicity [Cell Biology]
    [Aug 2014]

    Expansions of preexisting polyglutamine (polyQ) tracts in at least nine different proteins cause devastating neurodegenerative diseases. There are many unique features to these pathologies, but there must also be unifying mechanisms underlying polyQ toxicity. Using a polyQ-expanded fragment of huntingtin exon-1 (Htt103Q), the causal protein in Huntington disease, we and...
    Categories: Journal Articles
  • UBR5 is required for IR-induced ATM signaling [Cell Biology]
    [Aug 2014]

    The Mre11/Rad50/NBS1 (MRN) protein complex and ATMIN protein mediate ATM kinase signaling in response to ionizing radiation (IR) and chromatin changes, respectively. NBS1 and ATMIN directly compete for ATM binding, but the molecular mechanism favoring either NBS1 or ATMIN in response to specific stimuli is enigmatic. Here, we identify the...
    Categories: Journal Articles
  • Chondrocytes become osteoblasts in bone formation [Developmental Biology]
    [Aug 2014]

    According to current dogma, chondrocytes and osteoblasts are considered independent lineages derived from a common osteochondroprogenitor. In endochondral bone formation, chondrocytes undergo a series of differentiation steps to form the growth plate, and it generally is accepted that death is the ultimate fate of terminally differentiated hypertrophic chondrocytes (HCs). Osteoblasts,...
    Categories: Journal Articles
  • Experimental quantification of fracture energy [Engineering]
    [Aug 2014]

    Accurate measurement of interfacial properties is critical any time two materials are bonded—in composites, tooth crowns, or when biomaterials are attached to the human body. Yet, in spite of this importance, reliable methods to measure interfacial properties between dissimilar materials remain elusive. Here we present an experimental approach to quantify...
    Categories: Journal Articles
  • Dehalococcoides isolates respire on PCBs [Environmental Sciences]
    [Aug 2014]

    Fastidious anaerobic bacteria play critical roles in environmental bioremediation of halogenated compounds. However, their characterization and application have been largely impeded by difficulties in growing them in pure culture. Thus far, no pure culture has been reported to respire on the notorious polychlorinated biphenyls (PCBs), and functional genes responsible for...
    Categories: Journal Articles
  • Temperate origins of long-distance bird migration [Evolution]
    [Aug 2014]

    Migratory species exhibit seasonal variation in their geographic ranges, often inhabiting geographically and ecologically distinct breeding and nonbreeding areas. The complicated geography of seasonal migration has long posed a challenge for inferring the geographic origins of migratory species as well as evolutionary sequences of change in migratory behavior. To address...
    Categories: Journal Articles
  • Genetic bases of fitness tradeoffs [Evolution]
    [Aug 2014]

    Fitness tradeoffs are often assumed by evolutionary theory, yet little is known about the frequency of fitness tradeoffs during stress adaptation. Even less is known about the genetic factors that confer these tradeoffs and whether alternative adaptive mutations yield contrasting tradeoff dynamics. We addressed these issues using 114 clones of...
    Categories: Journal Articles
  • Domestication of defective prophages [Evolution]
    [Aug 2014]

    Integrated phages (prophages) are major contributors to the diversity of bacterial gene repertoires. Domestication of their components is thought to have endowed bacteria with molecular systems involved in secretion, defense, warfare, and gene transfer. However, the rates and mechanisms of domestication remain unknown. We used comparative genomics to study the...
    Categories: Journal Articles
  • PML-RAR blocks senescence to promote leukemia [Genetics]
    [Aug 2014]

    In most acute promyelocytic leukemia (APL) cases, translocons produce a promyelocytic leukemia protein–retinoic acid receptor α (PML–RARα) fusion gene. Although expression of the human PML fusion in mice promotes leukemia, its efficiency is rather low. Unexpectedly, we find that simply replacing the human PML fusion with its mouse counterpart results...
    Categories: Journal Articles
  • Regulation of lymphocyte retention by FAP+ FRCs [Immunology and Inflammation]
    [Aug 2014]

    Fibroblastic reticular cells (FRCs), through their expression of CC chemokine ligand (CCL)19 and CCL21, attract and retain T cells in lymph nodes (LNs), but whether this function applies to both resting and activated T cells has not been examined. Here we describe a model for conditionally depleting FRCs from LNs...
    Categories: Journal Articles
  • CD4 T-cell exhaustion in allograft tolerance [Immunology and Inflammation]
    [Aug 2014]

    Selectin–selectin ligand interactions mediate the initial steps in leukocyte migration, an integral part of immune responses. Fucosyltransferase-VII (FucT-VII), encoded by Fut7, is essential for biosynthesis of selectin ligands. In an established model of cardiac allograft vasculopathy and chronic rejection, Fut7−/− recipients exhibited long-term graft survival with minimal vasculopathy compared with...
    Categories: Journal Articles
  • HSC-independent B-1 cell development [Immunology and Inflammation]
    [Aug 2014]

    The fetal liver is a major hematopoietic site containing progenitor cells that give rise to nearly all blood cells, including B-1 cells. Because the fetal liver is not a de novo site of hematopoietic stem cell (HSC) or progenitor-cell emergence, it must be seeded by yolk sac (YS)-derived erythromyeloid progenitors...
    Categories: Journal Articles
  • Glutathionylation in the release of danger signals [Immunology and Inflammation]
    [Aug 2014]

    The mechanism by which oxidative stress induces inflammation and vice versa is unclear but is of great importance, being apparently linked to many chronic inflammatory diseases. We show here that inflammatory stimuli induce release of oxidized peroxiredoxin-2 (PRDX2), a ubiquitous redox-active intracellular enzyme. Once released, the extracellular PRDX2 acts as...
    Categories: Journal Articles