1H92

SH3 domain of human Lck tyrosine kinase

Summary for 1H92

• Entry DOI: 10.2210/pdb1h92/pdb
• Related: 1FBZ 1LCJ 1LCK 1QPC 1QPD 1QPE 1QPJ 3LCK
• Descriptor: PROTO-ONCOGENE TYROSINE-PROTEIN KINASE LCK (1 entity in total)
• Functional Keywords: transferase, sh3 domain, tyrosine kinase, signal transduction, lck
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P06239
• Total number of polymer chains: 1
• Total formula weight: 7008.68

Authors

Schweimer, K.,Hoffmann, S.,Friedrich, U.,Biesinger, B.,Roesch, P.,Sticht, H. (deposition date: 2001-02-22, release date: 2001-10-22, Last modification date: 2024-05-15)

Primary citation

Schweimer, K.,Hoffmann, S.,Bauer, F.,Friedrich, U.,Kardinal, C.,Feller, S.M.,Biesinger, B.,Sticht, H.
Structural Investigation of the Binding of a Herpesviral Protein to the SH3 Domain of Tyrosine Kinase Lck
Biochemistry, 41:5120-, 2002

PubMed 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.

PubMed: 11955060
DOI: 10.1021/BI015986J

Experimental method

SOLUTION NMR