Linked Life Data

15576028

Source:http://linkedlifedata.com/resource/pubmed/id/15576028

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2004-12-3
pubmed:abstractText
We test with molecular dynamics the hypothesis that interdomain forces in integrins, simulated with a spring attached to the C-terminal alpha 7-helix of an integrin I domain, can allosterically stabilize alternative I domain conformations. Depending on the force applied and timecourse, in alpha(L) and alpha(M) I domains the beta 6-alpha 7 loop moves successively between three ratchet positions; i.e. from closed to intermediate, and then to open. More distal, linked alterations in MIDAS loops and metal coordination closely resemble those seen when the MIDAS becomes ligated. Simulations show that the intermediate state is populated over a wider range of forces for alpha(L) than alpha(M) I domains. Simulations with mutant I domains suggest that specific ratchet residues regulate conformational equilibria. Simulations with alpha(1) and alpha(2) I domains reveal a lack of the intermediate conformation, owing to Phe to Glu substitution at the second ratchet residue. The findings have important implications for biological regulation of integrin adhesiveness.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0969-2126
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2137-47
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Conversion between three conformational states of integrin I domains with a C-terminal pull spring studied with molecular dynamics.
pubmed:affiliation
The CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.