Očuvanje točnosti biosinteze proteina: uloga popravka prije prijenosa aminokiseline na tRNA

undergraduate thesis

• Title (english): Maintaining fidelity of protein biosynthesis: the role of pretransfer editing
• Author: Sara Sumić
• Mentor: Ita Gruić-Sovulj (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2009, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Očuvanje točnosti biosinteze proteina je od iznimne važnosti za stanicu. Prvi korak u biosintezi proteina je sinteza odgovarajućeg para aminokiseline i tRNA pomoću aminoacil-tRNA-sintetaza (aaRS). Ti enzimi moraju prepoznati pripadnu aminokiselinu i tRNA, te u reakciji aminoacilacije prenijeti aminokiselinu na 3’ kraj tRNA. Odabir pripadne aminokiseline predstavlja problem nekim aminoacil-tRNA-sintetazama, pa one mogu aktivirati i nepripadne aminokiseline koje su kemijski, odnosno strukturno slične pripadnoj. U nekim slučajevima nepripadna aminokiselina se može prenijeti i na tRNA. Da bi se održao dovoljno visok stupanj točnosti biosinteze proteina, te su aminoacil-tRNA-sintetaze razvile dodatne hidrolitičke puteve popravka pogreške. Popravak se može odvijati prije ili poslije prijenosa aminokiseline na tRNA. U prvom slučaju hidrolizira se nepripadni aminoacil-adenilat (aktivirani oblik aminokiseline), a u drugom misacilirana tRNA (tRNA aminoacilirana nepripadnom aminokiselinom). Mnoge aaRS imaju prostorno odijeljenu domenu za popravak pogreške u kojoj dolazi do hidrolize misacilirane tRNA. Novija istraživanja na ovom polju dovode u pitanje predloženi mehanizam tRNA-ovisnog puta popravka koji se odvija prije prijenosa aminokiseline na tRNA. Neka od osnovnih pitanja na koja se još nastoji odgovoriti su: gdje se događa hidroliza nepripadnog aminoacil-adenilata, da li također u domeni za popravak ili unutar aktivnog mjesta? Koja je uloga pripadne tRNA u tom procesu? Budući da oba puta popravka imaju iste produkte i ovisnost o tRNA, teško ih je neovisno istraživati. Zbog toga je međusobni odnos dvaju puteva popravka još uvijek nepoznat kod većine aaRS. Ipak, metodama mehanističke enzimatologije nastoji se razjasniti mehanizam popravka pogreške prije prijenosa aminokiseline na tRNA, kao i njegova uloga u očuvanju točnosti biosinteze proteina.

Abstract (english)

Maintaining fidelity of protein biosynthesis is an essential feature of a cell. The first step of translation is synthesis of cognate amino acid:tRNA pairs by aminoacyl-tRNA synthetases (aaRS). These enzymes have to recognize and covalently link corresponding amino acid to its cognate tRNA. Selection of cognate amino acid represents a problem for some of aaRS, so they can misactivate near-cognate amino acids that are chemically and structurally similar to the cognate ones. In some cases, misactivated amino acid can be attached to tRNA. To maintain satisfying degree of translational quality, some aaRS have developed additional hydrolytic editing mechanisms to correct errors in the selection of amino acids. Editing can occur either before (pretransfer editing) or after aminoacylation to tRNA (posttransfer editing). In pretransfer editing, noncognate aminoacyl-adenylate is hydrolyzed, while in the posttransfer editing, misacylated tRNA is hydrolyzed. Many aaRS have separated and structurally distinct editing domain, where hydrolysis of misacylated tRNA takes place. With latest findings in this field of research, proposed mechanism for tRNA-dependent pretransfer editing becomes questionable. Some of the main issues are: where does aminoacyl-adenylate hydrolysis take place, within editing domain as misacylated tRNA, or within synthetic active site? What is the exact role for tRNA in that process? Both of the editing processes yield same final products, and both are tRNA dependent, so researches have difficulties with investigating them independently of one another. Still, mechanistic enzymology methods are used to further investigate pretransfer editing mechanism, and consequently to determine its role in maintaining fidelity of protein biosynthesis.

• Keywords: biosinteza proteina; prijenos aminokiseline na tRNA
• Language: croatian
• URN:NBN: urn:nbn:hr:217:795970
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-03-16 13:33:13