The structure of the human mitochondrial ribosome Amunts, Alexey; Brown, Alan; Toots, Jaan ...
Science (American Association for the Advancement of Science),
04/2015, Volume:
348, Issue:
6230
Journal Article
Peer reviewed
Open access
The highly divergent ribosomes of human mitochondria (mitoribosomes) synthesize 13 essential proteins of oxidative phosphorylation complexes. We have determined the structure of the intact ...mitoribosome to 3.5 angstrom resolution by means of single-particle electron cryogenic microscopy. It reveals 80 extensively interconnected proteins, 36 of which are specific to mitochondria, and three ribosomal RNA molecules. The head domain of the small subunit, particularly the messenger (mRNA) channel, is highly remodeled. Many intersubunit bridges are specific to the mitoribosome, which adopts conformations involving ratcheting or rolling of the small subunit that are distinct from those seen in bacteria or eukaryotes. An intrinsic guanosine triphosphatase mediates a contact between the head and central protuberance. The structure provides a reference for analysis of mutations that cause severe pathologies and for future drug design.
The recent rapid development of single‐particle electron cryo‐microscopy (cryo‐EM) now allows structures to be solved by this method at resolutions close to 3 Å. Here, a number of tools to facilitate ...the interpretation of EM reconstructions with stereochemically reasonable all‐atom models are described. The BALBES database has been repurposed as a tool for identifying protein folds from density maps. Modifications to Coot, including new Jiggle Fit and morphing tools and improved handling of nucleic acids, enhance its functionality for interpreting EM maps. REFMAC has been modified for optimal fitting of atomic models into EM maps. As external structural information can enhance the reliability of the derived atomic models, stabilize refinement and reduce overfitting, ProSMART has been extended to generate interatomic distance restraints from nucleic acid reference structures, and a new tool, LIBG, has been developed to generate nucleic acid base‐pair and parallel‐plane restraints. Furthermore, restraint generation has been integrated with visualization and editing in Coot, and these restraints have been applied to both real‐space refinement in Coot and reciprocal‐space refinement in REFMAC.
The highly divergent ribosomes of human mitochondria (mitoribosomes) synthesize 13 essential proteins of oxidative phosphorylation complexes. We have determined the structure of the intact ...mitoribosome to 3.5 angstrom resolution by means of single-particle electron cryogenic microscopy. It reveals 80 extensively interconnected proteins, 36 of which are specific to mitochondria, and three ribosomal RNA molecules. The head domain of the small subunit, particularly the messenger (mRNA) channel, is highly remodeled. Many intersubunit bridges are specific to the mitoribosome, which adopts conformations involving ratcheting or rolling of the small subunit that are distinct from those seen in bacteria or eukaryotes. An intrinsic guanosine triphosphatase mediates a contact between the head and central protuberance. The structure provides a reference for analysis of mutations that cause severe pathologies and for future drug design.
Ionic liquids (ILs) are known for their unique characteristics as solvents and electrolytes. Therefore, new ILs are being developed and adapted as innovative chemical environments for different ...applications in which their properties need to be understood on a molecular level. Computational data-driven methods provide means for understanding of properties at molecular level, and quantitative structure–property relationships (QSPRs) provide the framework for this. This framework is commonly used to study the properties of molecules in ILs as an environment. The opposite situation where the property is considered as a function of the ionic liquid does not exist. The aim of the present study was to supplement this perspective with new knowledge and to develop QSPRs that would allow the understanding of molecular interactions in ionic liquids based on the structure of the cationic moiety. A wide range of applications in electrochemistry, separation and extraction chemistry depends on the partitioning of solutes between the ionic liquid and the surrounding environment that is characterized by the gas-ionic liquid partition coefficient. To model this property as a function of the structure of a cationic counterpart, a series of ionic liquids was selected with a common bis-(trifluoromethylsulfonyl)-imide anion, Tf2N−, for benzene, hexane and cyclohexane. MLR, SVR and GPR machine learning approaches were used to derive data-driven models and their performance was compared. The cross-validation coefficients of determination in the range 0.71–0.93 along with other performance statistics indicated a strong accuracy of models for all data series and machine learning methods. The analysis and interpretation of descriptors revealed that generally higher lipophilicity and dispersion interaction capability, and lower polarity in the cations induces a higher partition coefficient for benzene, hexane, cyclohexane and hydrocarbons in general. The applicability domain analysis of models concluded that there were no highly influential outliers and the models are applicable to a wide selection of cation families with variable size, polarity and aliphatic or aromatic nature.
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•Gas-ionic liquid partition coefficient models relied on structure descriptors only.•Random forest (RF) models outperform multiple linear models (MLR) in most cases.•Descriptors ...selected for MLR models reflect specific solvent–solute interactions.•RF models descriptors compatibility with solvent–solute interactions is multifaceted.•Model diagnostics confirms models applicability to unknown organic compounds.
Ionic liquids (ILs) have unique properties as solvents and electrolytes, which need to be studied using innovative machine learning (ML) approaches and which allow the identification of a chemical environment that can be adapted to different applications. The gas-ionic liquid partition coefficients of organic compounds is one such application-oriented parameter for selecting both ionic liquids and organic compounds as quickly, cost-effectively, and as accurately as possible. Therefore, multiple linear regression (MLR) and random forest (RF) quantitative structure–property relationships (QSPRs) were developed for predicting the gas-ionic liquid partition coefficient (log K) of structurally variable organic solutes in the ionic liquids N-butyl-N-methylpyrrolidinium tris(pentafluoroethyl)trifluorophosphate (BMPyrr+FAP−), N-butyl-N-methylpyrrolidinium tricyanomethanide (BMPyrr+C(CN)3−) and 1-(2-methoxyethyl)-1-methylpyrrolidinium tris(pentafluoroethyl)trifluorophosphate (MeoeMPyrr+FAP−). All derived models have excellent prediction capability evidenced by high 5-fold cross-validated coefficients of determination in the range 0.88 – 0.94, complemented with other high statistical parameters. Compared to the MLR approach, the non-linear RF models statistics improved in two of three data series. Analysis of the molecular descriptors selected into MLR models revealed major solvent–solute interactions, with primary contributions from Coulomb and dipolar or hydrogen bonding interactions and followed by the descriptors that expose dispersion force related interactions. Relations to all the aforementioned solvent–solute interactions were also found in RF models descriptor interpretation. Comparison of models demonstrated that a common anion in different ILs produces a significant correlation between the data series log K values, while that of ILs with a common cation are less but still significantly correlated. The lower correlation could be attributed to varying structural differences in the corresponding ions, or the anion might have a more substantial role in determining partition properties with the organic solutes in the series.
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