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  • 1
    Online Resource
    Online Resource
    Structural changes in bacteriophage T7 upon receptor-induced genome ejection
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 37 ( 2021-09-14)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 37 ( 2021-09-14)
    Abstract: Many tailed bacteriophages assemble ejection proteins and a portal–tail complex at a unique vertex of the capsid. The ejection proteins form a transenvelope channel extending the portal–tail channel for the delivery of genomic DNA in cell infection. Here, we report the structure of the mature bacteriophage T7, including the ejection proteins, as well as the structures of the full and empty T7 particles in complex with their cell receptor lipopolysaccharide. Our near–atomic-resolution reconstruction shows that the ejection proteins in the mature T7 assemble into a core, which comprises a fourfold gene product 16 (gp16) ring, an eightfold gp15 ring, and a putative eightfold gp14 ring. The gp15 and gp16 are mainly composed of helix bundles, and gp16 harbors a lytic transglycosylase domain for degrading the bacterial peptidoglycan layer. When interacting with the lipopolysaccharide, the T7 tail nozzle opens. Six copies of gp14 anchor to the tail nozzle, extending the nozzle across the lipopolysaccharide lipid bilayer. The structures of gp15 and gp16 in the mature T7 suggest that they should undergo remarkable conformational changes to form the transenvelope channel. Hydrophobic α-helices were observed in gp16 but not in gp15, suggesting that gp15 forms the channel in the hydrophilic periplasm and gp16 forms the channel in the cytoplasmic membrane.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2102003118
    RVK:
    TA 1000
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
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  • 2
    Online Resource
    Online Resource
    Population-based 3D genome structure analysis reveals driving forces in spatial genome organization
    Proceedings of the National Academy of Sciences ; 2016
    In:  Proceedings of the National Academy of Sciences Vol. 113, No. 12 ( 2016-03-22)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 113, No. 12 ( 2016-03-22)
    Abstract: Conformation capture technologies (e.g., Hi-C) chart physical interactions between chromatin regions on a genome-wide scale. However, the structural variability of the genome between cells poses a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range and interchromosomal interactions. Here, we present a probabilistic approach for deconvoluting Hi-C data into a model population of distinct diploid 3D genome structures, which facilitates the detection of chromatin interactions likely to co-occur in individual cells. Our approach incorporates the stochastic nature of chromosome conformations and allows a detailed analysis of alternative chromatin structure states. For example, we predict and experimentally confirm the presence of large centromere clusters with distinct chromosome compositions varying between individual cells. The stability of these clusters varies greatly with their chromosome identities. We show that these chromosome-specific clusters can play a key role in the overall chromosome positioning in the nucleus and stabilizing specific chromatin interactions. By explicitly considering genome structural variability, our population-based method provides an important tool for revealing novel insights into the key factors shaping the spatial genome organization.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1512577113
    RVK:
    TA 1000
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2016
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  • 3
    Online Resource
    Online Resource
    Rice SPX1 and SPX2 inhibit phosphate starvation responses through interacting with PHR2 in a phosphate-dependent manner
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 41 ( 2014-10-14), p. 14953-14958
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 41 ( 2014-10-14), p. 14953-14958
    Abstract: In plants, sensing the levels of external and internal nutrients is essential for reprogramming the transcriptome and adapting to the fluctuating environment. Phosphate (Pi) is a key plant nutrient, and a large proportion of Pi starvation-responsive genes are under the control of PHOSPHATE STARVATION RESPONSE REGULATOR 1 (PHR1) in Arabidopsis (AtPHR1) and its homologs, such as Oryza sativa (Os)PHR2 in rice. AtPHR1 and OsPHR2 expression is not very responsive to Pi starvation, raising the question as to how plants sense changes in cellular Pi levels to activate the central regulator. SPX [named after SYG1 (suppressor of yeast gpa1 ), Pho81 (CDK inhibitor in yeast PHO pathway), and XPR1 (xenotropic and polytropic retrovirus receptor)] proteins that harbor only the SPX domain are reported to be involved in the negative regulation of Pi starvation responses. Here, we show that the nuclear localized SPX proteins SPX1 and SPX2 are Pi-dependent inhibitors of the activity of OsPHR2 in rice. Indeed, SPX1 and SPX2 proteins interact with PHR2 through their SPX domain, inhibiting its binding to P1BS (the PHR1-binding sequence: GNATATNC). In vivo data, as well as results from in vitro experiments using purified SPX1, SPX2, and OsPHR2 proteins, showed that SPX1 and SPX2 inhibition of OsPHR2 activity is Pi-dependent. These data provide evidence to support the involvement of SPX1 and SPX2 in the Pi-sensing mechanism in plants.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1404680111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
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  • 4
    Online Resource
    Online Resource
    Comprehensive tissue deconvolution of cell-free DNA by deep learning for disease diagnosis and monitoring
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 28 ( 2023-07-11)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 28 ( 2023-07-11)
    Abstract: Plasma cell-free DNA (cfDNA) is a noninvasive biomarker for cell death of all organs. Deciphering the tissue origin of cfDNA can reveal abnormal cell death because of diseases, which has great clinical potential in disease detection and monitoring. Despite the great promise, the sensitive and accurate quantification of tissue-derived cfDNA remains challenging to existing methods due to the limited characterization of tissue methylation and the reliance on unsupervised methods. To fully exploit the clinical potential of tissue-derived cfDNA, here we present one of the largest comprehensive and high-resolution methylation atlas based on 521 noncancer tissue samples spanning 29 major types of human tissues. We systematically identified fragment-level tissue-specific methylation patterns and extensively validated them in orthogonal datasets. Based on the rich tissue methylation atlas, we develop the first supervised tissue deconvolution approach, a deep-learning-powered model, cfSort , for sensitive and accurate tissue deconvolution in cfDNA. On the benchmarking data, cfSort showed superior sensitivity and accuracy compared to the existing methods. We further demonstrated the clinical utilities of cfSort with two potential applications: aiding disease diagnosis and monitoring treatment side effects. The tissue-derived cfDNA fraction estimated from cfSort reflected the clinical outcomes of the patients. In summary, the tissue methylation atlas and cfSort enhanced the performance of tissue deconvolution in cfDNA, thus facilitating cfDNA-based disease detection and longitudinal treatment monitoring.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2305236120
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
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  • 5
    Online Resource
    Online Resource
    The schizophrenia risk gene product miR-137 alters presynaptic plasticity
    Springer Science and Business Media LLC ; 2015
    In:  Nature Neuroscience Vol. 18, No. 7 ( 2015-07), p. 1008-1016
    Details
    In: Nature Neuroscience, Springer Science and Business Media LLC, Vol. 18, No. 7 ( 2015-07), p. 1008-1016
    Type of Medium: Online Resource
    ISSN: 1097-6256 , 1546-1726
    URL: Article
    DOI: 10.1038/nn.4023
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
    detail.hit.zdb_id: 1494955-6
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  • 6
    Online Resource
    Online Resource
    Automated multidimensional phenotypic profiling using large public microarray repositories
    Proceedings of the National Academy of Sciences ; 2009
    In:  Proceedings of the National Academy of Sciences Vol. 106, No. 30 ( 2009-07-28), p. 12323-12328
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 106, No. 30 ( 2009-07-28), p. 12323-12328
    Abstract: Phenotypes are complex, and difficult to quantify in a high-throughput fashion. The lack of comprehensive phenotype data can prevent or distort genotype–phenotype mapping. Here, we describe “PhenoProfiler,” a computational method that enables in silico phenotype profiling. Drawing on the principle that similar gene expression patterns are likely to be associated with similar phenotype patterns, PhenoProfiler supplements the missing quantitative phenotype information for a given microarray dataset based on other well-characterized microarray datasets. We applied our method to 587 human microarray datasets covering 〉 14,000 samples, and confirmed that the predicted phenotype profiles are highly consistent with true phenotype descriptions. PhenoProfiler offers several unique capabilities: ( i ) automated, multidimensional phenotype profiling, facilitating the analysis and treatment design of complex diseases; ( ii ) the extrapolation of phenotype profiles beyond provided classes; and ( iii ) the detection of confounding phenotype factors that could otherwise bias biological inferences. Finally, because no direct comparisons are made between gene expression values from different datasets, the method can use the entire body of cross-platform microarray data. This work has produced a compendium of phenotype profiles for the National Center for Biotechnology Information GEO datasets, which can facilitate an unbiased understanding of the transcriptome-phenome mapping. The continued accumulation of microarray data will further increase the power of PhenoProfiler, by increasing the variety and the quality of phenotypes to be profiled.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0900883106
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2009
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
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  • 7
    Online Resource
    Online Resource
    Tunable assembly of amyloid-forming peptides into nanosheets as a retrovirus carrier
    Proceedings of the National Academy of Sciences ; 2015
    In:  Proceedings of the National Academy of Sciences Vol. 112, No. 10 ( 2015-03-10), p. 2996-3001
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 10 ( 2015-03-10), p. 2996-3001
    Abstract: Using and engineering amyloid as nanomaterials are blossoming trends in bionanotechnology. Here, we show our discovery of an amyloid structure, termed “amyloid-like nanosheet,” formed by a key amyloid-forming segment of Alzheimer’s Aβ. Combining multiple biophysical and computational approaches, we proposed a structural model for the nanosheet that is formed by stacking the amyloid fibril spines perpendicular to the fibril axis. We further used the nanosheet for laboratorial retroviral transduction enhancement and directly visualized the presence of virus on the nanosheet surface by electron microscopy. Furthermore, based on our structural model, we designed nanosheet-forming peptides with different functionalities, elucidating the potential of rational design for amyloid-based materials with novel architecture and function.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1416690112
    RVK:
    TA 1000
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
    detail.hit.zdb_id: 209104-5
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  • 8
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    Online Resource
    Addendum: The schizophrenia risk gene product miR-137 alters presynaptic plasticity
    Springer Science and Business Media LLC ; 2016
    In:  Nature Neuroscience Vol. 19, No. 8 ( 2016-8), p. 1115-1115
    Details
    In: Nature Neuroscience, Springer Science and Business Media LLC, Vol. 19, No. 8 ( 2016-8), p. 1115-1115
    Type of Medium: Online Resource
    ISSN: 1097-6256 , 1546-1726
    URL: Article
    DOI: 10.1038/nn0816-1115c
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 1494955-6
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  • 9
    Online Resource
    Online Resource
    Nanoscale visualization and characterization of Myxococcus xanthus cells with atomic force microscopy
    Proceedings of the National Academy of Sciences ; 2005
    In:  Proceedings of the National Academy of Sciences Vol. 102, No. 18 ( 2005-05-03), p. 6484-6489
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 102, No. 18 ( 2005-05-03), p. 6484-6489
    Abstract: Multicellular microbial communities are the predominant form of existence for microorganisms in nature. As one of the most primitive social organisms, Myxococcus xanthus has been an ideal model bacterium for studying intercellular interaction and multicellular organization. Through previous genetic and EM studies, various extracellular appendages and matrix components have been found to be involved in the social behavior of M. xanthus , but none of them was directly visualized and analyzed under native conditions. Here, we used atomic force microscopy (AFM) imaging and in vivo force spectroscopy to characterize these cellular structures under native conditions. AFM imaging revealed morphological details on the extracellular ultrastructures at an unprecedented resolution, and in vivo force spectroscopy of live cells in fluid allowed us to nanomechanically characterize extracellular polymeric substances. The findings provide the basis for AFM as a useful tool for investigating microbial-surface ultrastructures and nanomechanical properties under native conditions.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0501207102
    RVK:
    TA 1000
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2005
    detail.hit.zdb_id: 209104-5
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  • 10
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    Online Resource
    Extracellular polysaccharides mediate pilus retraction during social motility of Myxococcus xanthus
    Proceedings of the National Academy of Sciences ; 2003
    In:  Proceedings of the National Academy of Sciences Vol. 100, No. 9 ( 2003-04-29), p. 5443-5448
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 9 ( 2003-04-29), p. 5443-5448
    Abstract: Myxococcus xanthus is a Gram-negative bacterium with a complex life cycle that includes vegetative swarming and fruiting-body formation. Social (S)-motility (coordinated movement of large cell groups) requires both type IV pili and fibrils (extracellular matrix material consisting of polysaccharides and protein). Little is known about the role of this extracellular matrix, or fibril material, in pilus-dependent motility. In this study, mutants lacking fibril material and, therefore, S-motility were found to be hyperpiliated. We demonstrated that addition of fibril material resulted in pilus retraction and rescued this phenotype. The fibril material was further examined to determine the component(s) that were responsible for triggering pilus retraction. Protein-free fibril material was found to be highly active in correcting hyperpiliation. However, the amine sugars present in hydrolyzed fibril material, e.g., glucosamine and N -acetylglucosamine (GlcNAc) had no effect on fibril − mutants, but, interestingly, cause hyperpiliation in wild-type cells. In contrast, chitin, a natural GlcNAc polymer, was found to restore pilus retraction in hyperpiliated mutants, indicating that a polysaccharide containing amine sugars is likely required for pilus retraction. These data suggest that the interaction of type IV pili with amine-containing polysaccharides on cell and slime-trail surfaces may trigger pilus retraction, resulting in S-motility and slime-trailing behaviors.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0836639100
    RVK:
    TA 1000
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2003
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
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