Signalling through ubiquitin ligase
Transcript of Signalling through ubiquitin ligase
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Signalling through Ubiquitin Ligase
Made by-Akum Paul Singh
Roll No.2084
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What happens during Stress?
An external factor that exerts a disadvantageous influence on plant Protein damage is a key event in the stress condition protein damage can be highly toxic causes the loss of function of that specific molecule the improper exposure of hydrophobic amino acid side chains, lead
to the aggregation of other proteins.
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How plants face protein degradation problem?
inducing the transcription of a set of genes whose products, known as stress proteins, enhance survival under stress conditions
Levels of damaged proteins can be reduced in two ways
On the one hand, specific molecular chaperones can prevent the aggregation of damaged proteins, and catalyze their refolding
On the other hand, specific proteases can degrade damaged proteins
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Scientist who discovered ubiquitin mediated proteolysis
Avram Hershko Aaron Ciechanover Irwin Rose
Nobel prize in chemistry, 2004
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Ubiquitin Consists of 76 amino
acids, 8.5 kDa Found in all
eukaryotic cells (ubiquitously)
Highly Conserved Used in post-
translational modification
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Small protein with big function
small, heat-stable, compact globular protein (76 AA)
Found only in eukaryotic organisms Highly conserved
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Ubiquitin Genes
UBA52 RPS27A UBB UBC
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Primary structure Met1-Gln2-Ile3-Phe4-Val5-Lys6-Thr7-Leu8-Thr9-Gly10-Lys11-
Thr12-Ile13-Thr14-Leu15-Glu16-Val17-Glu18-Pro19-Ser20-Asp21-Thr22-Ile23-
Glu24-Asn25-Val26-Lys27-Ala28-Lys29-Ile30-Gln31-Asp32-Lys33-Glu34-Gly35-Ile36-Pro37-Pro38-Asp39-Gln40-Gln41-Arg42-Leu43-Ile44-Phe45-
Ala46-Gly47-Lys48-Gln49-Leu50-Glu51-Asp52-Gly53-Arg54-Thr55-Leu56-
Ser57-Asp58-Tyr59-Asn60-Ile61-Gln62-Lys63-Glu64-Ser65-Thr66-Leu67-His68-Leu69-Val70-Leu71-Arg72-Leu73-Arg74-Gly75-Gly76
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Three types of Ubiquitination
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MonoubiquitinationAdds one ubiquitin molecule to one
substrate protein residueRequired before a poly chain can begin to
formMembrane Trafficking, Transcription,
Endocytosis
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PolyubiquitinationRequires one Ub linked to substrate before
chain begins to form.Chains made by linking Glysine residue of
Ub to a Lysine of a Ub bound to a substrate.
Linking to different position on Ub leads to different results.
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Lysine 48-linked polyubiquitinationLinked by 48th amino
acid (Lysine)Marks proteins for
destructionRequires at least 4 Ub to
be recognized by proteasome
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E3 ligasesThe most varied of the three enzymes.Each E3 can attach to many different substrate proteins. Different E2, E3 pairings will recognize different
proteins by distinct degradation signals.
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26S Proteasome Abundant in nucleus
and cytoplasm destroys proteins
marked by Ubiquitin through Lysine 48-linked polyubiquitination
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26S Proteasome Consists of central
hollow cylinder (20S) 4 stacked “rings” of 7
proteins each Capped by regulatory
particles (19S) that recognize ubiquitin through ubiquitin binding domains (UBDs)
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Ubiquitin in Protein Degradation
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Deubiquitinating enzyme (DUB) Around 100 in the
human genome Some cleave the whole
chain, some only cleave a set amount of Ubs
DUB USP5 selectively binds a 4-ubiquitin chain and severs it.
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Regulation of Protein Degradation
One means of controlling Ubiquitination is regulating the activation of E3 ligases.
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