Ubiquitin chains
From Proteopedia
(Difference between revisions)
| Line 9: | Line 9: | ||
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. | ||
| - | |||
| - | |||
| - | |||
| - | |||
| - | |||
== K63-linked ubiquitin chains == | == K63-linked ubiquitin chains == | ||
| - | <Structure load='3hm3' size='300' frame='true' align='left' caption='Structure of K63-linked tetraubiquitin in hte fully extended conformation, [[3hm3]]. ' scene='Insert optional scene name here' /> | ||
| - | K63-linked ubiquitin chains bound to proteins are associated with the DNA damage response and NF-κB signaling <ref>PMID: 21622571</ref>. In contrast to K48-linked tetraubiquitin, the structure of K63-linked ubiquitin is linear, with no inter-ubiquitin contacts apparent in the crystal <ref name=datta>PMID: 19664638</ref><ref>PMID: 19731378</ref>. Small angle X-ray scattering of K63-linked tetraubiquitin confirmed the observations from crystal structures but suggested that a small percentage of chains adopted a partially compacted structure <ref name=datta/>. The specific inter-ubiquitin contacts were not apparent from this experiment. The K63-linked ubiquitin chain binding domains in the signaling proteins NEMO <ref>PMID: 19766637</ref> and Rap80 <ref>PMID: 19536136</ref> bridge the hydrophobic patches of consecutive ubiquitins in the chain through a single alpha helix. The work of Sims and coworkers <ref>PMID: 19328070</ref> showed that decreasing the distance between the ubiquitin interacting motifs in Rap80 decreased the affinity of the Rap80 binding domain for the ubiquitin chain. | ||
| - | |||
| - | |||
| - | |||
| - | |||
| - | |||
| - | |||
| - | |||
| - | |||
| - | |||
| - | |||
| - | |||
| - | |||
| - | |||
| - | |||
| + | <scene name='45/459306/Cv/1'>K63-linked ubiquitin</scene> chains bound to proteins are associated with the DNA damage response and NF-κB signaling <ref>PMID: 21622571</ref>. In contrast to K48-linked tetraubiquitin, the structure of K63-linked ubiquitin is linear, with no inter-ubiquitin contacts apparent in the crystal <ref name=datta>PMID: 19664638</ref><ref>PMID: 19731378</ref>. Small angle X-ray scattering of K63-linked tetraubiquitin confirmed the observations from crystal structures but suggested that a small percentage of chains adopted a partially compacted structure <ref name=datta/>. The specific inter-ubiquitin contacts were not apparent from this experiment. The K63-linked ubiquitin chain binding domains in the signaling proteins NEMO <ref>PMID: 19766637</ref> and Rap80 <ref>PMID: 19536136</ref> bridge the hydrophobic patches of consecutive ubiquitins in the chain through a single alpha helix. The work of Sims and coworkers <ref>PMID: 19328070</ref> showed that decreasing the distance between the ubiquitin interacting motifs in Rap80 decreased the affinity of the Rap80 binding domain for the ubiquitin chain. | ||
== K11-linked ubiquitin chains == | == K11-linked ubiquitin chains == | ||
| Line 50: | Line 30: | ||
== Chains of Ubiquitin-like proteins (Ubls) == | == Chains of Ubiquitin-like proteins (Ubls) == | ||
| - | < | + | |
| + | <scene name='45/459306/Cv/2'>'Structure of a ISG15 monomer. The tertiary structure consists of two ubiquitin-like folds, resembling a molecule of diubiquitin</scene> ([[1z2m]]). | ||
| + | |||
SUMO (Small Ubiquitin-like Modifying Object) does form chains<ref>PMID: 11451954</ref>, however no structural information on these chains is available. Chains of other Ubls may exist, but there is not significant data on their structure and function. The tertiary structure of ISG15 is comprised of two beta grasp folds and is similar in appearance to diubiquitin <ref>PMID: 15917233</ref>. Whether this influences the function of ISG15 is not clear at this time. | SUMO (Small Ubiquitin-like Modifying Object) does form chains<ref>PMID: 11451954</ref>, however no structural information on these chains is available. Chains of other Ubls may exist, but there is not significant data on their structure and function. The tertiary structure of ISG15 is comprised of two beta grasp folds and is similar in appearance to diubiquitin <ref>PMID: 15917233</ref>. Whether this influences the function of ISG15 is not clear at this time. | ||
Revision as of 13:23, 23 July 2013
| |||||||||||
