6 research outputs found

    Phylogenetic correlations can suffice to infer protein partners from sequences

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    International audienceDetermining which proteins interact together is crucial to a systems-level understanding of the cell. Recently, algorithms based on Direct Coupling Analysis (DCA) pairwise maximum-entropy models have allowed to identify interaction partners among paralogous proteins from sequence data. This success of DCA at predicting protein-protein interactions could be mainly based on its known ability to identify pairs of residues that are in contact in the three-dimensional structure of protein complexes and that coevolve to remain physicochemically complementary. However, interacting proteins possess similar evolutionary histories. What is the role of purely phylogenetic correlations in the performance of DCA-based methods to infer interaction partners? To address this question, we employ controlled synthetic data that only involve phylogeny and no interactions or contacts. We find that DCA accurately identifies the pairs of synthetic sequences that share evolutionary history. While phylogenetic correlations confound the identification of contacting residues by DCA, they are thus useful to predict interacting partners among paralogs. We find that DCA performs as well as phylogenetic methods to this end, and slightly better than them with large and accurate training sets. Employing DCA or phylogenetic methods within an Iterative Pairing Algorithm (IPA) allows to predict pairs of evolutionary partners without a training set. We further demonstrate the ability of these various methods to correctly predict pairings among real paralogous proteins with genome proximity but no known direct physical interaction, illustrating the importance of phylogenetic correlations in natural data. However, for physically interacting and strongly coevolving proteins, DCA and mutual information outperform phylogenetic methods. We finally discuss how to distinguish physically interacting proteins from proteins that only share a common evolutionary history

    Synergistic defects in pre-rRNA processing from mutations in the U3-specific protein Rrp9 and U3 snoRNA

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    International audienceU3 snoRNA and the associated Rrp9/U3-55K protein are essential for 18S rRNA production by the SSU-processome complex. U3 and Rrp9 are required for early pre-rRNA cleavages at sites A0, A1 and A2, but the mechanism remains unclear. Substitution of Arg 289 in Rrp9 to Ala (R289A) specifically reduced cleavage at sites A1 and A2. Surprisingly, R289 is located on the surface of the Rrp9 β-propeller structure opposite to U3 snoRNA. To understand this, we first characterized the protein-protein interaction network of Rrp9 within the SSU-processome. This identified a direct interaction between the Rrp9 β-propeller domain and Rrp36, the strength of which was reduced by the R289A substitution, implicating this interaction in the observed processing phenotype. The Rrp9 R289A mutation also showed strong synergistic negative interactions with mutations in U3 that destabilize the U3/pre-rRNA base-pair interactions or reduce the length of their linking segments. We propose that the Rrp9 β-propeller and U3/pre-rRNA binding cooperate in the structure or stability of the SSU-processome. Additionally, our analysis of U3 variants gave insights into the function of individual segments of the 5'-terminal 72-nt sequence of U3. We interpret these data in the light of recently reported SSU-processome structures

    The CORALIE survey for southern extrasolar planets XIX: Brown dwarfs and stellar companions unveiled by radial velocity and astrometry

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    A historical planet-search on a sample of 1647 nearby southern main sequence stars has been ongoing since 1998 with the CORALIE spectrograph at La Silla Observatory, with a backup subprogram dedicated to the monitoring of binary stars. We review 25 years of CORALIE measurements and search for Doppler signals consistent with stellar or brown dwarf companions to produce an updated catalog of both known and previously unpublished binary stars in the planet-search sample, assessing the binarity fraction of the stellar population and providing perspective for more precise planet-search in the binary sample. We perform new analysis on the CORALIE planet-search sample radial velocity measurements, searching for stellar companions and obtaining orbital solutions for both known and new binary systems. We perform simultaneous radial velocity and proper motion anomaly fits on the subset of these systems for which Hipparcos and Gaia astrometry measurements are available, obtaining accurate estimates of true mass for the companions. We find 218 stars in the CORALIE sample to have at least one stellar companion, 130 of which are not yet published in the literature and for which we present orbital solutions. The use of proper motion anomaly allow us to derive true masses for the stellar companions in 132 systems, which we additionally use to estimate stability regions for possible planetary companions on circumprimary or circumbinary orbits. Finally, we produce detection limit maps for each star in the sample and obtain occurrence rates of 0.430.11+0.23%0.43^{+0.23}_{-0.11}\% and 12.690.77+0.87%12.69^{+0.87}_{-0.77}\% for brown dwarf and stellar companions respectively in the CORALIE sample.ISSN:0004-6361ISSN:1432-074

    Hasan, Environment from the molecular level: an escience testbed project, AHM 2003

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    The testbed project has the ambition to push the practical possibilities of atomistic simulations forward to the point where we can perform realistic calculations on important environmental processes. The project has three components: the science driving the project, the development of the simulation codes, and setting up a grid infrastructure for this work. This paper describes these areas of work and gives a status report on each. 1
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