Linked Life Data

10213605

Source:http://linkedlifedata.com/resource/pubmed/id/10213605

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
1999-5-7
pubmed:abstractText
The cytosolic tyrosine kinase Syk is recruited to immune cell receptors via interactions of its tandem-SH2 domain with tyrosine-phosphorylated sequences called immune receptor tyrosine activation motifs (ITAMs). We have characterized the binding of the tandem-SH2 domain of Syk (Syk-tSH2) to a dually phosphorylated peptide derived from the ITAM of the T cell receptor CD3-epsilon subunit. The CD3-epsilon peptide binds with an affinity of 18-81 nM at 150 mM NaCl over the 4.5-30 degrees C temperature range that was studied. The enthalpy of binding, DeltaH degrees obs, shows an unusual nonlinear dependence on temperature, suggesting the possibility of a temperature-dependent conformational equilibrium coupled to binding. This hypothesis was tested and confirmed by examining the temperature dependence of (1) the on-rate constant for binding and (2) the fluorescence of Syk-tSH2 and its CD3-epsilon peptide complex. The DeltaH degrees obs, Kobs, fluorescence, and kinetic data are all well described by a model incorporating the hypothesized conformational equilibrium. Circular dichroism spectra at various temperatures indicate that the conformational change is not due to a partial unfolding of the protein. We suggest that the conformational equilibrium enables Syk-tSH2 to exhibit flexibility in its binding modality, which may be necessitated by Syk's involvement in a wide variety of signal tranduction pathways.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5024-33
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:10213605-Antigens, CD3, pubmed-meshheading:10213605-Circular Dichroism, pubmed-meshheading:10213605-Enzyme Precursors, pubmed-meshheading:10213605-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:10213605-Kinetics, pubmed-meshheading:10213605-Models, Chemical, pubmed-meshheading:10213605-Models, Molecular, pubmed-meshheading:10213605-Oligopeptides, pubmed-meshheading:10213605-Phosphorylation, pubmed-meshheading:10213605-Protein Binding, pubmed-meshheading:10213605-Protein Conformation, pubmed-meshheading:10213605-Protein-Tyrosine Kinases, pubmed-meshheading:10213605-Receptors, Amino Acid, pubmed-meshheading:10213605-Receptors, Antigen, T-Cell, pubmed-meshheading:10213605-Temperature, pubmed-meshheading:10213605-Thermodynamics, pubmed-meshheading:10213605-Tyrosine, pubmed-meshheading:10213605-src Homology Domains
pubmed:year
1999
pubmed:articleTitle
Thermodynamic study of the binding of the tandem-SH2 domain of the Syk kinase to a dually phosphorylated ITAM peptide: evidence for two conformers.
pubmed:affiliation
Department of Biochemistry, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't