Effect of antibiotics on ribosome assembly is indirect
Date
2011-05-03
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Abstract
Bakteriaalne ribosoom moodustub kolmest erinevast ribosoomi RNA-st ja rohkem kui 50 ribosoomi valgust. Varasemalt oli teada, et mitmed valgusünteesi inhibiitorid inhibeerivad ka ribosoomide kokkupakkimist ja põhjustavad ribosomaalsete eellaspartiklite kuhjumist rakkudes. Selle protsessi selgitamiseks on esitatud kaks erinevat mudelit. Arvatakse, et antibiootikumi klooramfenikool inhibeeriv mõju ribosoomide kokkupakkimisele on kaude ja tuleneb valgusünteesi inhibeerimisest. Teise mudel kohaselt seondud antibiootikum erütromütsiin ribosoomide eellaspartiklitele ja inhibeerib ribosoomide kokkupakkimist otseselt. Oleme uurinud ribosoomide kokkupakkimise defekte kummagi antibiootikumi juuresolekul kasutades erinevaid eksperimentaalseid lähenemisi. Oleme tõestanud, et nii erütromüstiin kui ka klooramfenikool inhibeerivad ribosoomide kokkupakkimist kaudselt, see tähendab valgusünteesi inhibeerimise kaudu. Rakkude töötlemine erütromütsiini või klooramfenikooliga põhjustab ribosoomi valkude tasakaalustamata sünteesi. Ribosoomi valkude erinev kättesaadavus rakus määrab omakorda ribosoomide kokkupakkimise edenemise ning on selgituseks ribosomaalsete eellaspartiklite kuhjumisele.
Bacterial ribosome is assembled from three different ribosomal RNAs and more than 50 ribosomal proteins. Several protein synthesis inhibitors are known to inhibit assembly of the procaryotic ribosome and to cause accumulation of ribosomal precursor particles. Two alternative models exist to explain this phenomenon. Firstly, antibiotic chloramphenicol is thought to inhbit ribosome assembly as a secondary effect of protein synthesis inhibition. Secondly, antibiotic erythromycin is thought to inhibit assembly directly by binding to ribosome assembly intermediate. We have studied ribosome assembly defects in the presence of erythromycin and chloramphenicol with several different experimental approaches. In conclusion, we found that both erythromycin and chloramphenicol inhibt ribosome assembly indirectly due to protein syntheisis inhibition. The treatment of cells with chloramphenicol or erythromycin leads to unbalanced synthesis of ribosomal proteins, the availability of different ribosomal proteins determines the coure of ribosome assembly and provides the explanation for formation of assembly-defective particle.
Bacterial ribosome is assembled from three different ribosomal RNAs and more than 50 ribosomal proteins. Several protein synthesis inhibitors are known to inhibit assembly of the procaryotic ribosome and to cause accumulation of ribosomal precursor particles. Two alternative models exist to explain this phenomenon. Firstly, antibiotic chloramphenicol is thought to inhbit ribosome assembly as a secondary effect of protein synthesis inhibition. Secondly, antibiotic erythromycin is thought to inhibit assembly directly by binding to ribosome assembly intermediate. We have studied ribosome assembly defects in the presence of erythromycin and chloramphenicol with several different experimental approaches. In conclusion, we found that both erythromycin and chloramphenicol inhibt ribosome assembly indirectly due to protein syntheisis inhibition. The treatment of cells with chloramphenicol or erythromycin leads to unbalanced synthesis of ribosomal proteins, the availability of different ribosomal proteins determines the coure of ribosome assembly and provides the explanation for formation of assembly-defective particle.
Description
Väitekirja elektrooniline versioon ei sisalda publikatsioone.
Keywords
dissertatsioonid, bioloogia, antibiootikumid, ribosoomid, translatsioon (biol.), ribosoomid, inhibitsioon, translation (biol.), ribosomes, inhibition, antibiotics