Ubiquitin Structure & Function: Difference between revisions
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=== Ubiquitin Conjugation === | === Ubiquitin Conjugation === | ||
The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly. | The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly. | ||
[[Image:diubq.png| thumb |none | upright=2.0 |Isopeptide bond between two Ubiquitin molecules]] | [[Image:diubq.png| thumb |none | upright=2.0 |Isopeptide bond between two Ubiquitin molecules]][[Image:Ubq_pathway.png| thumb |right | upright=2.0 |Ubiquitinylation pathway]] | ||
Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition. | Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition. | ||
=== Proofreading === | === Proofreading === | ||
Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a "futile cycle"<ref name="Ubproteindeg">PMID: 3022650</ref>. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin<ref name="regulation">PMID: 9409543</ref>. | Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a "futile cycle"<ref name="Ubproteindeg">PMID: 3022650</ref>. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin<ref name="regulation">PMID: 9409543</ref>. | ||
=== Conjugate Metabolism === | === Conjugate Metabolism === | ||
If, however, the target protein is found to be damaged, the ubiquitinylated protein is lead to its degradation by the 26S proteasome<ref>Hochstrasser, M. 1996. Ubiquitin-dependent protein Degradation. Annu Rev Genet. 30: 405-439</ref>. The 26S proteasome is made up of a 20S core and a 19S cap. The targeted protein must be unfolded, deubiquitinylated and translocated through the 19S cap channels and into the proteasome interior. The 20S proteasome than cleaves the polypeptide into short peptides of roughly 7-9 fragment residues. This process is ATP-independent. Cytosolic peptidases then degrades the fragment into its appropriate amino acids. The ubiquitin molecules are returned to the cell where they are reused. | If, however, the target protein is found to be damaged, the ubiquitinylated protein is lead to its degradation by the 26S proteasome<ref>Hochstrasser, M. 1996. Ubiquitin-dependent protein Degradation. Annu Rev Genet. 30: 405-439</ref>. The 26S proteasome is made up of a 20S core and a 19S cap. The targeted protein must be unfolded, deubiquitinylated and translocated through the 19S cap channels and into the proteasome interior. The 20S proteasome than cleaves the polypeptide into short peptides of roughly 7-9 fragment residues. This process is ATP-independent. Cytosolic peptidases then degrades the fragment into its appropriate amino acids. The ubiquitin molecules are returned to the cell where they are reused.[[Image:proteosome length.png| thumb |none | upright=0.75 |Length view of Proteasome]][[Image:proteaosome top.png| thumb |left | upright=1.0 |Top view of proteasome]] | ||
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=Types of Ubiquitin Conjugates= | =Types of Ubiquitin Conjugates= | ||
