Linked Life Data

19813706

Source:http://linkedlifedata.com/resource/pubmed/id/19813706

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
2009-10-22
pubmed:abstractText
As the initial step of the entry of HIV-1 into cells, the interaction of CD4 with gp120 is a central area of concern in HIV-1 biology and intervention studies. CD4 binding induces large conformational changes to gp120, such as the formation of the bridging sheet between the V1/V2 stem and beta20/beta21. Understanding the dynamic process and the mechanism that leads to the formation of the bridging sheet is important. We have studied the formation of the bridging sheet via extensive molecular dynamics simulations on a modeled intermediate state. The intermediate state is derived from the crystal structure of the gp120/CD4 complex with rotation of the alpha1 helix and separation of the V1/V2 stem from beta20/beta21. The molecular dynamics simulations reveal that CD4-bound gp120 leads to the refolding of the bridging sheet but the CD4-free gp120 leads to structures similar to unliganded structures of SIV gp120. The bridging sheet refolds with the S375W mutant, but it does not refold with the W112A and S375W/T257S mutants. Our simulation results are in agreement with experimental observations, and they reveal the importance of the formation of the hydrophobic core to the conformational change of CD4-induced gp120. Other experimental observations, including variations in the binding entropy in different mutants, are also qualitatively reproduced.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1520-5207
pubmed:author
pubmed:issnType
Electronic
pubmed:day
29
pubmed:volume
113
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14536-43
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Understanding of the bridging sheet formation of HIV-1 glycoprotein gp120.
pubmed:affiliation
Laboratory of Chemical Genomics, Shenzhen Graduate School of Peking University, Shenzhen 518055, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't