Automatic Prediction of Protein 3D Structures by Probabilistic Multi-template Homology Modeling

Meier, Armin; Söding, Johannes

doi:10.1371/journal.pcbi.1004343

Cited by 120 publications

(95 citation statements)

References 30 publications

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“…Bootstrap values were calculated for 10,000 trials. A hidden Markov model-based search was performed for the alignment using HHpred (Meier and Söding, 2015). Significant structural similarity was found between CLAMP and Claudin-19 ( p = 4.1 × 10 −9 ), Claudin-15 ( p = 7.3 × 10 −9 ), and the voltage-gated calcium channel γ subunit 15 ( p = 10 −10 ), which all belong to the same tetraspan family (Simske, 2013).…”

Section: Methods and Resourcesmentioning

confidence: 99%

A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes

Sidik

Huet

Ganesan

et al. 2016

Cell

683

108

1,001

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SUMMARY Apicomplexan parasites are leading causes of human and livestock diseases—like malaria and toxoplasmosis—yet most of their genes remain uncharacterized. Here, we present the first genome-wide genetic screen of an apicomplexan. We adapted CRISPR/Cas9 to assess the contribution of each gene from the human parasite Toxoplasma gondii during infection of fibroblasts. Our analysis defines ~200 previously uncharacterized, fitness-conferring genes unique to the phylum, from which 16 were investigated, revealing essential functions during infection of human cells. Secondary screens identify as an invasion factor the claudin-like apicomplexan microneme protein (CLAMP), which resembles mammalian tight-junction proteins and localizes to secretory organelles, making it critical to the initiation of infection. CLAMP is present throughout sequenced apicomplexan genomes, and is essential during the asexual stages of the malaria parasite Plasmodium falciparum. These results provide broad-based functional information on T. gondii genes and will facilitate future approaches to expand the horizon of antiparasitic interventions.

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Section: Methods and Resourcesmentioning

confidence: 99%

A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes

Sidik

Huet

Ganesan

et al. 2016

Cell

683

108

1,001

View full text Add to dashboard Cite

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“…In the next step, we applied profile analysis to find and merge groups of related sequences. For this purpose, sequences in each group were aligned with Muscle (52) (default parameters), and the alignments were used to predict secondary structure and build profiles with the tools "addss" and "hhmake" available in the HHsuite package (53). The collection of profiles was enriched with those generated previously (47) for a large number of (nonarchaeal) dsDNA viruses.…”

Section: Classification Of Genes Into Homologous Familiesmentioning

confidence: 99%

Bipartite Network Analysis of the Archaeal Virosphere: Evolutionary Connections between Viruses and Capsidless Mobile Elements

Iranzo

Koonin

Prangishvili

et al. 2016

J Virol

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Archaea and particularly hyperthermophilic crenarchaea are hosts to many unusual viruses with diverse virion shapes and distinct gene compositions. As is typical of viruses in general, there are no universal genes in the archaeal virosphere. Therefore, to obtain a comprehensive picture of the evolutionary relationships between viruses, network analysis methods are more productive than traditional phylogenetic approaches. Here we present a comprehensive comparative analysis of genomes and proteomes from all currently known taxonomically classified and unclassified, cultivated and uncultivated archaeal viruses. We constructed a bipartite network of archaeal viruses that includes two classes of nodes, the genomes and gene families that connect them. Dissection of this network using formal community detection methods reveals strong modularity, with 10 distinct modules and 3 putative supermodules. However, compared to similar previously analyzed networks of eukaryotic and bacterial viruses, the archaeal virus network is sparsely connected. With the exception of the tailed viruses related to bacteriophages of the order Caudovirales and the families Turriviridae and Sphaerolipoviridae that are linked to a distinct supermodule of eukaryotic and bacterial viruses, there are few connector genes shared by different archaeal virus modules. In contrast, most of these modules include, in addition to viruses, capsidless mobile elements, emphasizing tight evolutionary connections between the two types of entities in archaea. The relative contributions of distinct evolutionary origins, in particular from nonviral elements, and insufficient sampling to the sparsity of the archaeal virus network remain to be determined by further exploration of the archaeal virosphere. V iruses infecting archaea are among the most mysterious denizens of the virosphere. Archaeal viruses display a rich diversity of virion morphotypes and can be broadly divided into two categories: those that are structurally and genetically related to bacterial or eukaryotic viruses and those that are archaeon specific (1-4). The cosmopolitan fraction of archaeal viruses includes (i) head-tailed viruses of the order Caudovirales, with the 3 included families, Siphoviridae, Myoviridae, and Podoviridae; (ii) tailless icosahedral viruses of the families Sphaerolipoviridae and Turriviridae; and (iii) enveloped pleomorphic viruses of the family Pleolipoviridae. All of these viruses, except for those of the family Turriviridae, propagate in members of the archaeal phylum Euryarchaeota, whereas most of the archaeon-specific virus groups infect hyperthermophilic organisms of the phylum Crenarchaeota.The order Caudovirales contains three families, the Siphoviridae, Myoviridae, and Podoviridae, and includes both bacterial and archaeal viruses. Members of the Caudovirales feature icosahedral capsids and helical tails attached to one of the vertices of the capsid. These viruses have been largely isolated from hyperhalophilic archaea (order Halobacteriales), although one...

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“…The crystal structure of nakanori at 1.5‐A resolution was determined by molecular replacement (42) using a trimmed ensemble of 3 distant homologs as initial search model. The trimmed ensemble was generated by superimposing the top 3 results of an HHpred search (43, 44), trimming diverging residues and leaving the conserved core. This provided a clear solution for one molecule in P 6 5 , which was refined to a final R work : R free ratio of 0.1833:0.2185 with the Phenix program suite (ver.…”

Section: Methodsmentioning

confidence: 99%

A novel sphingomyelin/cholesterol domain‐specific probe reveals the dynamics of the membrane domains during virus release and in Niemann‐Pick type C

et al. 2016

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We identified a novel, nontoxic mushroom protein that specifically binds to a complex of sphingomyelin (SM), a major sphingolipid in mammalian cells, and cholesterol (Chol). The purified protein, termed nakanori, labeled cell surface domains in an SM- and Chol-dependent manner and decorated specific lipid domains that colocalized with inner leaflet small GTPase H-Ras, but not K-Ras. The use of nakanori as a lipid-domain-specific probe revealed altered distribution and dynamics of SM/Chol on the cell surface of Niemann-Pick type C fibroblasts, possibly explaining some of the disease phenotype. In addition, that nakanori treatment of epithelial cells after influenza virus infection potently inhibited virus release demonstrates the therapeutic value of targeting specific lipid domains for anti-viral treatment.-Makino, A., Abe, M., Ishitsuka, R., Murate, M., Kishimoto, T., Sakai, S., Hullin-Matsuda, F., Shimada, Y., Inaba, T., Miyatake, H., Tanaka, H., Kurahashi, A., Pack, C.-G., Kasai, R. S., Kubo, S., Schieber, N. L., Dohmae, N., Tochio, N., Hagiwara, K., Sasaki, Y., Aida, Y., Fujimori, F., Kigawa, T., Nishibori, K., Parton, R. G., Kusumi, A., Sako, Y., Anderluh, G., Yamashita, M., Kobayashi, T., Greimel, P., Kobayashi, T. A novel sphingomyelin/cholesterol domain-specific probe reveals the dynamics of the membrane domains during virus release and in Niemann-Pick type C.

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Automatic Prediction of Protein 3D Structures by Probabilistic Multi-template Homology Modeling

Cited by 120 publications

References 30 publications

A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes

A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes

Bipartite Network Analysis of the Archaeal Virosphere: Evolutionary Connections between Viruses and Capsidless Mobile Elements

A novel sphingomyelin/cholesterol domain‐specific probe reveals the dynamics of the membrane domains during virus release and in Niemann‐Pick type C

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