Structural basis of the auto-inhibition mechanism of nonreceptor tyrosine kinase PTK6

Sunggeon Ko, Kyo Eun Ahn, Young Min Lee, Hee Chul Ahn, Weontae Lee

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4 Citations (Scopus)


Protein tyrosine kinase 6 (PTK6) is composed of SH3, SH2, and Kinase domains, with a linker region (Linker) between the SH2 and Kinase domains. Here, we report the structural basis of the SH3-Linker interaction that results in auto-inhibition of PTK6. The solution structures of the SH3 domain and SH3/Linker complex were determined by NMR spectroscopy. The structure of the SH3 domain forms a conventional β-barrel with two β-sheets comprised of five β-strands. However, the molecular topology and charge distribution of PTK6-SH3 slightly differs from that of the other SH3 domains. The structure of the N-terminal Linker within the complex showed that the proline-rich region (P175-P187) of the Linker forms a compact hairpin structure through hydrophobic interactions. The structure of the SH3/Linker complex revealed intra-molecular interaction between the amino acid pairs R22/E190, W44/W184, N65/P177, and Y66/P179. Mutations in PTK6 at R22, W44, N65, and Y66 residues in the SH3 domain increased catalytic activity compared with wild-type protein, implying that specific interactions between hydrophobic residues in the proline-rich linker region and hydrophobic residues in the SH3 domain are mainly responsible for down-regulating the catalytic activity of PTK6.

Original languageEnglish
Pages (from-to)236-242
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 2009 Jun 26

Bibliographical note

Funding Information:
This work was supported by a Grant (No. 070292) from the National R&D program for Cancer Control from the Ministry of Health & Welfare. This work was also supported in part by the Brain Korea 21 Project.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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