Linked Life Data

18045872

Source:http://linkedlifedata.com/resource/pubmed/id/18045872

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-1-28
pubmed:abstractText
Ligand binding induces shape changes within the four modular ectodomains (D1-D4) of the CD4 receptor, an important receptor in immune signaling. Small angle x-ray scattering (SAXS) on both a two-domain and a four-domain construct of the soluble CD4 (sCD4) is consistent with known crystal structures demonstrating a bilobal and a semi-extended tetralobal Z conformation in solution, respectively. Detection of conformational changes within sCD4 as a result of ligand binding was followed by SAXS on sCD4 bound to two different glycoprotein ligands: the tick saliva immunosuppressor Salp15 and the HIV-1 envelope protein gp120. Ab initio modeling of these data showed that both Salp15 and gp120 bind to the D1 domain of sCD4 and yet induce drastically different structural rearrangements. Upon binding, Salp15 primarily distorts the characteristic lobal architecture of the sCD4 without significantly altering the semi-extended shape of the sCD4 receptor. In sharp contrast, the interaction of gp120 with sCD4 induces a shape change within sCD4 that can be described as a Z-to-U bi-fold closure of the four domains across its flexible D2-D3 linker. Placement of known crystal structures within the boundaries of the SAXS-derived models suggests that the ligand-induced shape changes could be a result of conformational changes within this D2-D3 linker. Functionally, the observed shape changes in CD4 receptor causes dissociation of lymphocyte kinase from the cytoplasmic domain of Salp15-bound CD4 and facilitates an interaction between the exposed V3 loops of CD4-bound gp120 molecule to the extracellular loops of its co-receptor, a step essential for HIV-1 viral entry.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2761-72
pubmed:dateRevised
2011-5-5
pubmed:meshHeading
pubmed-meshheading:18045872-Animals, pubmed-meshheading:18045872-Antigens, CD4, pubmed-meshheading:18045872-HIV Envelope Protein gp120, pubmed-meshheading:18045872-Humans, pubmed-meshheading:18045872-Ligands, pubmed-meshheading:18045872-Lymphocyte Activation, pubmed-meshheading:18045872-Mice, pubmed-meshheading:18045872-Mice, Inbred BALB C, pubmed-meshheading:18045872-Mice, Inbred C3H, pubmed-meshheading:18045872-Models, Molecular, pubmed-meshheading:18045872-Protein Conformation, pubmed-meshheading:18045872-Protein Structure, Tertiary, pubmed-meshheading:18045872-Recombinant Proteins, pubmed-meshheading:18045872-Salivary Proteins and Peptides, pubmed-meshheading:18045872-Scattering, Small Angle, pubmed-meshheading:18045872-Solubility, pubmed-meshheading:18045872-T-Lymphocytes, pubmed-meshheading:18045872-X-Ray Diffraction
pubmed:year
2008
pubmed:articleTitle
Conformational rearrangement within the soluble domains of the CD4 receptor is ligand-specific.
pubmed:affiliation
Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural