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PDBsum entry 1h92
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural investigation of the binding of a herpesviral protein to the sh3 domain of tyrosine kinase lck.
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Authors
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K.Schweimer,
S.Hoffmann,
F.Bauer,
U.Friedrich,
C.Kardinal,
S.M.Feller,
B.Biesinger,
H.Sticht.
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Ref.
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Biochemistry, 2002,
41,
5120-5130.
[DOI no: ]
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PubMed id
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Abstract
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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.
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