Ubiquitin chains
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| + | <StructureSection load='' size='450' side='right' scene='45/459306/K48_chain_dimer/2' caption=''> | ||
| + | |||
'''Ubiquitin''' chains (or polyubiquitin chains) are protein post-translational modifications that regulate proteasome dependent protein degradation, the cellular response to DNA damage, the inflammatory response and other cellular functions <ref>PMID: 19217402</ref><ref>PMID: 9367341</ref>. Chains begin as a single ubiquitin attached to the modified protein via an isopeptide linkage between a lysine side chain within the substrate protein and the C-terminal glycine of ubiquitin. The chain is built and extended by ubiquitination of ubiquitin on one of the lysines of ubiquitin or the N-terminus. There are a total of seven lysines in ubiquitin (K6, K11, K27, K29, K33, K48, and K63) and chains using all seven lysines have been identified <ref name=Xu>PMID: 19345192</ref>. Chains are frequently referred to in the literature by the lysine position in ubiquitin that connects one ubiquitin to the next. For example, chains built on lysine 48 of ubiquitin are called K48-linked chains. N-terminal to C-terminal connection of ubiquitin molecules is called a linear ubiquitin chain and chains which contain linkages through several lysine positions are called mixed chains <ref>PMID: 18516089</ref>. Ubiquitin chains with different linkages can have different cellular functions some of which are summarized below. The basis for the functional differences between polyubiquitin chains of different linkages were not apparent until the X-ray and NMR structures of several chains were solved. | '''Ubiquitin''' chains (or polyubiquitin chains) are protein post-translational modifications that regulate proteasome dependent protein degradation, the cellular response to DNA damage, the inflammatory response and other cellular functions <ref>PMID: 19217402</ref><ref>PMID: 9367341</ref>. Chains begin as a single ubiquitin attached to the modified protein via an isopeptide linkage between a lysine side chain within the substrate protein and the C-terminal glycine of ubiquitin. The chain is built and extended by ubiquitination of ubiquitin on one of the lysines of ubiquitin or the N-terminus. There are a total of seven lysines in ubiquitin (K6, K11, K27, K29, K33, K48, and K63) and chains using all seven lysines have been identified <ref name=Xu>PMID: 19345192</ref>. Chains are frequently referred to in the literature by the lysine position in ubiquitin that connects one ubiquitin to the next. For example, chains built on lysine 48 of ubiquitin are called K48-linked chains. N-terminal to C-terminal connection of ubiquitin molecules is called a linear ubiquitin chain and chains which contain linkages through several lysine positions are called mixed chains <ref>PMID: 18516089</ref>. Ubiquitin chains with different linkages can have different cellular functions some of which are summarized below. The basis for the functional differences between polyubiquitin chains of different linkages were not apparent until the X-ray and NMR structures of several chains were solved. | ||
| + | == K48-linked ubiquitin chains == | ||
| - | - | + | <scene name='Ubiquitin_chains/K48_chain_dimer/1'>K48-linked tetraubiquitin</scene> ([[2o6v]]). |
| - | |||
| - | |||
| - | == K48-linked ubiquitin chains == | ||
| - | <Structure load='2o6v' size='300' frame='true' align='right' caption='K48-linked tetraubiquitin, [[2o6v]]' scene='Ubiquitin_chains/K48_chain_dimer/1' /> | ||
K48-linked ubiquitin chains are the primary signal for proteasome dependent degradation of proteins. The attachment of a chain of four or more ubiquitin molecules to a protein is required for efficient degradation. The X-ray crystal structure of K-48 linked diubiquitin<ref name=cook>PMID:1322903</ref> showed inter-ubiquitin interactions between the <scene name='Ubiquitin_chains/K48_chain/2'>hydrophobic patches</scene>(residues L8, I44, V70) of the two molecules. A later X-ray crystal structure of K48-linked tetraubiquitin<ref>PMID: 8107144</ref> showed that the ubiquitin chain adopted a globular tertiary structure which has been described as a <scene name='Ubiquitin_chains/K48_chain_dimer/1'>dimer of ubiquitin dimers </scene>. The interactions between the hydrophobic patches of ubiquitin molecules in 1 and 2 or 3 and 4 were similar to those observed in the diubiquitin structure <ref name=cook/>. | K48-linked ubiquitin chains are the primary signal for proteasome dependent degradation of proteins. The attachment of a chain of four or more ubiquitin molecules to a protein is required for efficient degradation. The X-ray crystal structure of K-48 linked diubiquitin<ref name=cook>PMID:1322903</ref> showed inter-ubiquitin interactions between the <scene name='Ubiquitin_chains/K48_chain/2'>hydrophobic patches</scene>(residues L8, I44, V70) of the two molecules. A later X-ray crystal structure of K48-linked tetraubiquitin<ref>PMID: 8107144</ref> showed that the ubiquitin chain adopted a globular tertiary structure which has been described as a <scene name='Ubiquitin_chains/K48_chain_dimer/1'>dimer of ubiquitin dimers </scene>. The interactions between the hydrophobic patches of ubiquitin molecules in 1 and 2 or 3 and 4 were similar to those observed in the diubiquitin structure <ref name=cook/>. | ||
Since the initial structure, several K48-linked tetraubiquitin crystal structures <ref>PMID: 11173499</ref> <ref name=eddins>PMID: 17240395</ref> <ref>PMID: 20823512</ref> have shown there are slight rearrangements of the tertiary structure of the chain dependent upon the pH of the crystallization solution. At pH 6.7, the chain adopts what is known as the closed conformation, because the chain remains in a largely compact form. At pH values less than 4.5, the interaction between diubiquitin molecules becomes weaker and the chain is less compact and there are fewer inter-ubiquitin contacts <ref name=eddins/>. The different tertiary conformations of the polyubiquitin chain are thought to be indicative of the dynamics of the K48-linked ubiquitin chain in the cell. These changes would allow ubiquitin binding proteins to interact with the hydrophobic patches of the ubiquitin molecules<ref>PMID: 9485444</ref>. The structure of cyclic K48-linked tetraubiquitin adopts the same dimer of ubiquitin dimer structure seen in the linear chains <ref>PMID: 20728431</ref>. The authors of this structure suggest this structure demonstrates the inherent flexibility of the ubiquitin chain. | Since the initial structure, several K48-linked tetraubiquitin crystal structures <ref>PMID: 11173499</ref> <ref name=eddins>PMID: 17240395</ref> <ref>PMID: 20823512</ref> have shown there are slight rearrangements of the tertiary structure of the chain dependent upon the pH of the crystallization solution. At pH 6.7, the chain adopts what is known as the closed conformation, because the chain remains in a largely compact form. At pH values less than 4.5, the interaction between diubiquitin molecules becomes weaker and the chain is less compact and there are fewer inter-ubiquitin contacts <ref name=eddins/>. The different tertiary conformations of the polyubiquitin chain are thought to be indicative of the dynamics of the K48-linked ubiquitin chain in the cell. These changes would allow ubiquitin binding proteins to interact with the hydrophobic patches of the ubiquitin molecules<ref>PMID: 9485444</ref>. The structure of cyclic K48-linked tetraubiquitin adopts the same dimer of ubiquitin dimer structure seen in the linear chains <ref>PMID: 20728431</ref>. The authors of this structure suggest this structure demonstrates the inherent flexibility of the ubiquitin chain. | ||
Revision as of 13:18, 23 July 2013
| |||||||||||
