Mehanizmi kontrole pravilnog smatanja proteina

undergraduate thesis

• Title (english): Control mechanisms governing protein folding
• Author: Dona Vuković
• Mentor: Maja Matulić (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2022-09-22, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Biološka funkcija proteina uvelike ovisi o njihovoj konformaciji, stoga je proces smatanja
kojim proteini poprimaju pravilnu trodimenzionalnu strukturu iznimno vaţan i kontroliran u
stanici. Smatanje je potpomognuto molekularnim šaperonima koji stupaju u interakciju s
novosintetiziranim proteinima. Endoplazmatski retikulum (ER) vaţan je organel u kojem se
smata i doraĎuje gotovo trećina staničnih proteina. Ukoliko je njegova homeostaza narušena
dolazi do nakupljanja nesmotanih proteina i stanja poznatog kao stres endoplazmatskog
retikuluma. Posljedično dolazi do aktivacije odgovora na nesmotane proteine (UPR),
staničnog obrambenog mehanizma koji nastoji smanjiti količinu nesmotanih proteina u ER-u.
ProvoĎenje signala inducirano je senzornim proteinima smještenima u membrani ER-a. Kod
kvasca je to protein Ire1, a kod Metazoa IRE1, PERK i ATF6. Rezultat signalne kaskade je
povećana transkripcija gena čiji su produkti uključeni u smatanje proteina i sintezu membrane
ER-a, ali i smanjenje sinteze staničnih proteina. UPR regulira i proces degradacije povezane s
endoplazmatskim retikulumom (ERAD) za proteine koji ne mogu biti pravilno smotani.
Ispravno funkcioniranje navedenih mehanizama vaţno je za organizam budući da nakupljanje
nesmotanih proteina i formiranje proteinskih agregata moţe uzrokovati mnoge bolesti.

Abstract (english)

Biological function of proteins largely depends on their conformation, therefore the folding
process by which proteins arrange in a proper three-dimensional structure is extremely
important and controlled in the cell. Folding is assisted by molecular chaperones that interact
with newly synthesized proteins. The endoplasmic reticulum (ER) is an important organelle in
which almost a third of cellular proteins are folded and modified. If ER homeostasis is
disturbed, unfolded proteins accumulate in its lumen leading to a condition known as
endoplasmic reticulum stress. As a result, a cellular defense mechanism known as the
unfolded protein response (UPR) is activated. UPR strives to reduce the content of unfolded
proteins in the ER. Signal transduction is induced by sensory proteins located in the ER
membrane. Ire1 is present in yeast, and proteins IRE1, PERK and ATF6 are present in
Metazoans. The result of the signaling cascade is increased transcription of genes whose
products are involved in protein folding and ER membrane synthesis, and also reduction of
global protein synthesis. If protein cannot be properly folded, it is degraded by the process
called endoplasmic reticulum-associated protein degradation (ERAD) which is also regulated
by the UPR. Proper functioning of these mechanisms is important for the organism since the
accumulation of unfolded proteins and formation of protein aggregates can cause various
diseases.

• Keywords: stres endoplazmatskog retikuluma; odgovor na nesmotane proteine; IRE1; PERK; ATF6; degradacija proteina povezana s endoplazmatskim retikulumom
• Keywords (english): endoplasmic reticulum stress; unfolded protein response; IRE1; PERK; ATF6; endoplasmic reticulum-associated protein degradation
• Language: croatian
• URN:NBN: urn:nbn:hr:217:019702
• 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: 2022-09-26 14:09:25