Linked Life Data

8617744

Source:http://linkedlifedata.com/resource/pubmed/id/8617744

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1996-6-11
pubmed:abstractText
The N-terminal 200 amino acids of SHC constitute a unique phosphotyrosine (Tyr(P)) interaction (PI) domain that shows no significant sequence similarity to the other Tyr(P)-recognizing module, the SH2 domain. We describe the thermodynamic parameters characterizing PI domain binding to various tyrosyl phosphopeptides, using isothermal titration calorimetry. The PI domain forms 1:1 complexes of similar affinity with a 12-mer peptide (ISLDNPDpYQQDF) derived from Tyr-1148 of the epidermal growth factor receptor (EGFR) (KD = 28 nm) and an 18-mer (LQGHIIENPQpYFSDACVH) derived from Tyr-490 of Trk (KD = 42 nM). Binding of the EGFR-derived peptide was largely enthalpy-driven at 25 degrees C, while Trk490 peptide binding was entropy-driven. Based on the change in heat capacity upon binding, approximately 700 A2 of nonpolar surface was estimated to be buried upon interaction. Alteration of the Asn or Pro to Ala in the NPXpY motif of the EGFR Tyr-1148 peptide increased the KD of PI domain interactions to 238 and 370 nM, respectively. Alteration of a Leu at position -5 (with respect to Tyr(P)) in the EGFR peptide to Gly also reduced the binding affinity (KD = 580 nM). It is proposed that the PI domain recognizes the beta1 turn that is found in NPXpY-containing peptides and also interacts with a larger segment of the peptide than seen for SH2 domains.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4770-5
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:8617744-Adaptor Proteins, Signal Transducing, pubmed-meshheading:8617744-Adaptor Proteins, Vesicular Transport, pubmed-meshheading:8617744-Amino Acid Sequence, pubmed-meshheading:8617744-Binding Sites, pubmed-meshheading:8617744-Calorimetry, pubmed-meshheading:8617744-Glutathione Transferase, pubmed-meshheading:8617744-Molecular Sequence Data, pubmed-meshheading:8617744-Mutagenesis, Site-Directed, pubmed-meshheading:8617744-Peptide Fragments, pubmed-meshheading:8617744-Phosphotyrosine, pubmed-meshheading:8617744-Point Mutation, pubmed-meshheading:8617744-Protein Biosynthesis, pubmed-meshheading:8617744-Proteins, pubmed-meshheading:8617744-Receptor, Epidermal Growth Factor, pubmed-meshheading:8617744-Recombinant Fusion Proteins, pubmed-meshheading:8617744-Shc Signaling Adaptor Proteins, pubmed-meshheading:8617744-Thermodynamics, pubmed-meshheading:8617744-src Homology Domains
pubmed:year
1996
pubmed:articleTitle
Thermodynamic studies of SHC phosphotyrosine interaction domain recognition of the NPXpY motif.
pubmed:affiliation
Department of Pharmacology, New York University Medical Center, New York, New York 10016, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't