Linked Life Data

18300229

Source:http://linkedlifedata.com/resource/pubmed/id/18300229

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-7-15
pubmed:abstractText
Eph receptors and ephrins constitute the largest family of receptor tyrosine kinases with 15 individual receptors and nine ligands. Its ectodomains represent attractive targets not only for understanding fundamental mechanisms underlying axon guidance, cell migration, segmentation, tumorigenesis, and bone remodeling, but also for drug screening/design to treat cancers, bone diseases and viral infection. So far no NMR study on the ephrin ectodomains is available and as such their properties in solution still remain unknown. In this study, we presented the first NMR structure and dynamics of the human ephrin-B2 ectodomain as well as its interaction with the receptor EphB2. Strikingly, the NMR study reveals a picture different from those previously obtained by X-ray crystallography. Although in solution it still adopts the same Greek key fold, with the central beta-barrel ( approximately 30% of the molecule) highly similar to that in crystal structures, the other regions are highly dynamic and accessible to the bulk solvent. In particular, the functionally critical C-D and G-H loops of the ephrin-B2 ectodomain are highly flexible as reflected by several NMR probes including hydrogen exchange and (15)N backbone relaxation data. Nevertheless, as revealed by ITC and NMR, the ephrin-B2 ectodomain binds to EphB2 with a K(d) of 22.3 nM to form a tight complex in which the tip of the C-D loop and the C-terminus still remain largely flexible. The present results may bear critical implications in understanding the molecular details as well as designing antagonists of therapeutic interest for Eph-ephrin interactions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1097-0134
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1019-29
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
NMR structure and dynamics of human ephrin-B2 ectodomain: the functionally critical C-D and G-H loops are highly dynamic in solution.
pubmed:affiliation
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't