Structural investigation of the binding of a herpesviral protein to the SH3 domain of tyrosine kinase Lck.

Details

Serval ID
serval:BIB_045FB3F14CBC
Type
Article: article from journal or magazin.
Collection
Publications
Title
Structural investigation of the binding of a herpesviral protein to the SH3 domain of tyrosine kinase Lck.
Journal
Biochemistry
Author(s)
Schweimer K., Hoffmann S., Bauer F., Friedrich U., Kardinal C., Feller S.M., Biesinger B., Sticht H.
ISSN
0006-2960
Publication state
Published
Issued date
2002
Peer-reviewed
Oui
Volume
41
Number
16
Pages
5120-30
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
Herpesvirus saimiri codes for a tyrosine kinase interacting protein (Tip) that interacts with both the SH3 domain and the kinase domain of the T-cell-specific tyrosine kinase Lck via two separate motifs. The activation of Lck by Tip is considered as a key event in the transformation of human T-lymphocytes during herpesviral infection. We investigated the interaction of proline-rich Tip peptides with the LckSH3 domain starting with the structural characterization of the unbound interaction partners. The solution structure of the LckSH3 was determined by heteronuclear multidimensional nuclear magnetic resonance (NMR) spectroscopy using 44 residual dipolar couplings in addition to the conventional experimental restraints. Circular dichroism spectroscopy proved that the polyproline helix of Tip is already formed prior to SH3 binding and is conformationally stable. NMR titration experiments point out three major regions of the Tip-Lck interaction comprising the RT loop, the n-src loop, and a helical turn preceding the last strand of the beta-sheet. Further changes of the chemical shifts were observed for the N- and C-terminal beta-strands of the SH3 domain, indicating additional contacts outside the proline-rich segment or subtle structural rearrangements transmitted from the binding site of the proline helix. Fluorescence spectroscopy shows that Tip binds to the SH3 domains of several Src kinases (Lck, Hck, Lyn, Src, Fyn, Yes), exhibiting the highest affinities for Lyn, Hck, and Lck.
Keywords
Amino Acid Sequence, Carbon Isotopes, Circular Dichroism, Computer Simulation, Crystallography, X-Ray, Herpesvirus 2, Saimiriine, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Models, Molecular, Molecular Sequence Data, Nitrogen Isotopes, Nuclear Magnetic Resonance, Biomolecular, Phosphoproteins, Protein Binding, Protons, Spectrometry, Fluorescence, Thermodynamics, Viral Proteins, src Homology Domains
Pubmed
Web of science
Create date
08/10/2008 9:58
Last modification date
20/08/2019 12:26
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