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| - | [[Image:2qnj.jpg|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2qnj| PDB=2qnj | SCENE= }} | | {{STRUCTURE_2qnj| PDB=2qnj | SCENE= }} |
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| - | '''Kinase and Ubiquitin-associated domains of MARK3/Par-1'''
| + | ===Kinase and Ubiquitin-associated domains of MARK3/Par-1=== |
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| - | ==Overview==
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| - | The Par-1/MARK protein kinases play a pivotal role in establishing cellular polarity. This family of kinases contains a unique domain architecture, in which a ubiquitin-associated (UBA) domain is located C-terminal to the kinase domain. We have used a combination of x-ray crystallography and NMR dynamics experiments to understand the interaction of the human (h) MARK3 UBA domain with the adjacent kinase domain as compared with ubiquitin. The x-ray crystal structure of the linked hMARK3 kinase and UBA domains establishes that the UBA domain forms a stable intramolecular interaction with the N-terminal lobe of the kinase domain. However, solution-state NMR studies of the isolated UBA domain indicate that it is highly dynamic, undergoing conformational transitions that can be explained by a folding-unfolding equilibrium. NMR titration experiments indicated that the hMARK3 UBA domain has a detectable but extremely weak affinity for mono ubiquitin, which suggests that conformational instability of the isolated hMARK3 UBA domain attenuates binding to ubiquitin despite the presence of residues typically involved in ubiquitin recognition. Our data identify a molecular mechanism through which the hMARK3 UBA domain has evolved to bind the kinase domain, in a fashion that stabilizes an open conformation of the N- and C-terminal lobes, at the expense of its capacity to engage ubiquitin. These results may be relevant more generally to the 30% of UBA domains that lack significant ubiquitin-binding activity, and they suggest a unique mechanism by which interaction domains may evolve new binding properties. | + | The line below this paragraph, {{ABSTRACT_PUBMED_17726107}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17726107 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17726107}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Transferase]] | | [[Category: Transferase]] |
| | [[Category: Ubiquitin-associated domain]] | | [[Category: Ubiquitin-associated domain]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 15:15:10 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:27:52 2008'' |
Revision as of 04:27, 28 July 2008
Template:STRUCTURE 2qnj
Kinase and Ubiquitin-associated domains of MARK3/Par-1
Template:ABSTRACT PUBMED 17726107
About this Structure
2QNJ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Conformational instability of the MARK3 UBA domain compromises ubiquitin recognition and promotes interaction with the adjacent kinase domain., Murphy JM, Korzhnev DM, Ceccarelli DF, Briant DJ, Zarrine-Afsar A, Sicheri F, Kay LE, Pawson T, Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14336-41. Epub 2007 Aug 28. PMID:17726107
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