The pleiotropic functions of ribosomal proteins eL19 and eL24 in the budding yeast ribosome
Failid
Kuupäev
2019-07-08
Autorid
Ajakirja pealkiri
Ajakirja ISSN
Köite pealkiri
Kirjastaja
Abstrakt
Valkude biosüntees on kõige enam energiat tarbiv protsess rakus. Seetõttu on loogiline, et häired selles protsessis mõjutavad raku füsioloogiat negatiivselt ja põhjustavad mitmesuguseid haigusi. Valke sünteesivad suured makromolekulaarsed kompleksid – ribosoomid. Kuigi nende ülesehituse ja toimimise põhimõtteid on kaua uuritud, on paljud ribosoomidega seotud aspektid veel ebaselged. Struktuuriuuringud näitavad, et ribosoomid koosnevad kõikides eluslooduse domeenides (Bacteria, Archaea ja Eukarya) RNA-st ja valkudest, mis moodustavad väikese ja suure ribosomaalse alaühiku. Eukarüoodi ribosoomi iseloomustab ulatuslik valkude vaheliste interaktsioonide võrgustik. Selle oluline osa on kontaktid ribosomaalsete alaühikute vahel: sillad, mis tagavad alaühikute liikumise valgusünteesi käigus ning seega kindlustavad ribosoomi optimaalse funktsioneerimise. Käesoleva uurimistöö raames uuriti kahte interaktsioonide võrgustikku kuuluvat ribosomaalset valku - eL19 ja eL24. Mõlemad valgud koosnevad kolmest struktuursest domeenist, mida saab jagada esiteks arhe- ja eukarüoodispetsiifilisteks ning teiseks eukarüoodispetsiifilisteks. Valkude eL19 ja eL24 mutatsioonianalüüsil selgus, et nende arhele ja eukarüoodile eriomased domeenid tagavad suure ribosomaalse alaühiku struktuuri korrektse moodustamise. Eukarüoodile eriomased domeenid ulatuvad suurest alaühikust kaugele ja osalevad alaühikutevaheliste sildade eB12 ja eB13 moodustamisel. Käesolevas töös näidatakse esmakordselt, et need sillad toetavad efektiivset valgusünteesi, stabiliseerides ribosomaalsete alaühikute koospüsimist. Kokkuvõtteks saab järeldada, et valkude eL19 ja eL24 funktsioonid on jagatud nende struktuursete domeenide vahel. Saadud tulemused laiendavad meie teadmisi sellest, kuidas ribosoomi ülesehitus on seotud tema funktsiooniga.
Protein biosynthesis is known to be the dominant energy consuming process in cells. It is no wonder that alterations in this process disturb cell physiology and lead to a variety of diseases. Proteins are exclusively synthesized by large macromolecular complexes called ribosomes. Ribosome structure and mechanism of their function have been extensively studied, but many aspects of the ribosomal machinery are still obscure. Structural studies demonstrate that in all domains of life (Bacteria, Archaea and Eukarya) ribosomes consist of RNAs and proteins that are organized into a small and a large ribosomal subunit. Structure of the eukaryotic ribosome is distinctive by a comprehensive neuron-like network of interactions between ribosomal proteins. An important part of this network is assigned to contacts between ribosomal subunit – intersubunit bridges that guide movements of subunits during protein synthesis. Two ribosomal proteins, eL19 and eL24, are in the focus of the present study. Both proteins consist of three structural domains that can be divided into archaea/eukaryote-specific and eukaryote-specific domains. Mutational analysis of eL19 and eL24 revealed that archaea/eukaryote-specific domains ensure formation of the proper structure of the large ribosomal subunit. The eukaryote-specific domains of eL19 and eL24 extend far from the large ribosomal subunit and form intersubunit bridges eB12 and eB13, respectively. The data show for the first time that eukaryote-specific bridges eB12 and eB13 support protein synthesis by stabilizing the association of ribosomal subunits. The current thesis demonstrates that archaea/eukaryote-specific and eukaryote-specific domains of proteins eL19 and eL24 bear distinctive functions. Altogether, a link between structural organization and functionality of the eukaryotic ribosomes is uncovered in this study
Protein biosynthesis is known to be the dominant energy consuming process in cells. It is no wonder that alterations in this process disturb cell physiology and lead to a variety of diseases. Proteins are exclusively synthesized by large macromolecular complexes called ribosomes. Ribosome structure and mechanism of their function have been extensively studied, but many aspects of the ribosomal machinery are still obscure. Structural studies demonstrate that in all domains of life (Bacteria, Archaea and Eukarya) ribosomes consist of RNAs and proteins that are organized into a small and a large ribosomal subunit. Structure of the eukaryotic ribosome is distinctive by a comprehensive neuron-like network of interactions between ribosomal proteins. An important part of this network is assigned to contacts between ribosomal subunit – intersubunit bridges that guide movements of subunits during protein synthesis. Two ribosomal proteins, eL19 and eL24, are in the focus of the present study. Both proteins consist of three structural domains that can be divided into archaea/eukaryote-specific and eukaryote-specific domains. Mutational analysis of eL19 and eL24 revealed that archaea/eukaryote-specific domains ensure formation of the proper structure of the large ribosomal subunit. The eukaryote-specific domains of eL19 and eL24 extend far from the large ribosomal subunit and form intersubunit bridges eB12 and eB13, respectively. The data show for the first time that eukaryote-specific bridges eB12 and eB13 support protein synthesis by stabilizing the association of ribosomal subunits. The current thesis demonstrates that archaea/eukaryote-specific and eukaryote-specific domains of proteins eL19 and eL24 bear distinctive functions. Altogether, a link between structural organization and functionality of the eukaryotic ribosomes is uncovered in this study
Kirjeldus
Väitekirja elektrooniline versioon ei sisalda publikatsioone
Märksõnad
ribosoomid, Saccharomyces cerevisiae, ribosoomivalgud, rRNA, interaktsioonid, translatsioon (biol.)