Linked Life Data

18411422

Source:http://linkedlifedata.com/resource/pubmed/id/18411422

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-5-28
pubmed:databankReference
pubmed:abstractText
Leukemia-associated Rho guanine nucleotide exchange factor (LARG) is a RhoA-specific guanine nucleotide exchange factor (GEF) that can activate RhoA. The PDZ (PSD-95/Disc-large/ZO-1 homology) domain of LARG interacts with membrane receptors, which can relay extracellular signals to RhoA signal transduction pathways. Until now there is no structural and dynamic information about these interactions. Here we report the NMR structures of the LARG PDZ in the apo form and in complex with the plexin-B1 C-terminal octapeptide. Unobservable resonances of the residues in betaB/betaC and betaE/alphaB loops in apo state were observed in the complex state. A distinct region of the binding groove in the LARG PDZ was found to undergo conformational change compared with other PDZs. Analysis of the (15)N relaxation data using reduced spectral density mapping shows that the apo LARG PDZ (especially its ligand-binding groove) is flexible and exhibits internal motions on both picosecond to nanosecond and microsecond to millisecond timescales. Mutagenesis and thermodynamic studies indicate that the conformation of the betaB/betaC and betaE/alphaB loops affects the PDZ-peptide interaction. It is suggested that the conformational flexibility could facilitate the change of structures upon ligand binding.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-10212987, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-10520995, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-10637762, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-10681437, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-10718609, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-10872457, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-11373293, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-11462815, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-11724822, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-11749973, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-11911894, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-12101119, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-12123608, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-12196542, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-12196628, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-12444095, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-12446668, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-12842047, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-1390643, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-14698303, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-15297673, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-15303831, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-15331592, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-15684424, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-15811367, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-16478718, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-16565089, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-17002371, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-17020769, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-17069616, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-17098254, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-17161370, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-17279591, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-17279777, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-2223770, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-2690953, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-7514039, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-7888179, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-8377180, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-8520220, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-8589604, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-8974395, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-9008363, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-9533918, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-9647694, http://linkedlifedata.com/resource/pubmed/commentcorrection/18411422-9757107
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1469-896X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1003-14
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Conformational change upon ligand binding and dynamics of the PDZ domain from leukemia-associated Rho guanine nucleotide exchange factor.
pubmed:affiliation
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't