title: Backbone nuclear relaxation characteristics and calorimetric investigation of the human Grb7-SH2/erbB2 peptide complex.
abstract: Grb7 is a member of the Grb7 family of proteins, which also includes Grb10 and Grb14. All three proteins have been found to be overexpressed in certain cancers and cancer cell lines. In particular, Grb7 (along with the receptor tyrosine kinase erbB2) is overexpressed in 20%-30% of breast cancers. Grb7 binds to erbB2 and may be involved in cell signaling pathways that promote the formation of metastases and inflammatory responses. In a prior study, we reported the solution structure of the Grb7-SH2/erbB2 peptide complex. In this study, T(1), T(2), and steady-state NOE measurements were performed on the Grb7-SH2 domain, and the backbone relaxation behavior of the domain is discussed with respect to the potential function of an insert region present in all three members of this protein family. Isothermal titration calorimetry (ITC) studies were completed measuring the thermodynamic parameters of the binding of a 10-residue phosphorylated peptide representative of erbB2 to the SH2 domain. These measurements are compared to calorimetric studies performed on other SH2 domain/phosphorylated peptide complexes available in the literature.
authors.affiliation: Department of Biochemistry, College of Medicine, University of Vermont, Burlington 05405, USA.
authors.forename: Monika
authors.initials: M
authors.lastname: Ivancic
authors.forename: Anne M
authors.initials: AM
authors.lastname: Spuches
authors.forename: Ethan C
authors.initials: EC
authors.lastname: Guth
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Daugherty
authors.forename: Dean E
authors.initials: DE
authors.lastname: Wilcox
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Lyons
mesh_terms: D051382:GRB7 Adaptor Protein; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry*; D013816:Thermodynamics; D018909:src Homology Domains
chemical_list: D051382:GRB7 Adaptor Protein; D046912:Multiprotein Complexes; D010455:Peptides; D011506:Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C495955:GRB7 protein, human