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

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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
Volume384
Issue number2
DOIs
Publication statusPublished - 2009 Jun 26

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src Homology Domains
Protein-Tyrosine Kinases
Proline
Catalyst activity
Phosphotransferases
Hydrophobic and Hydrophilic Interactions
Molecular interactions
Charge distribution
Nuclear magnetic resonance spectroscopy
Topology
Amino Acids
Magnetic Resonance Spectroscopy
Mutation
Proteins

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ko, Sunggeon ; Ahn, Kyo Eun ; Lee, Young Min ; Ahn, Hee Chul ; Lee, Weontae. / Structural basis of the auto-inhibition mechanism of nonreceptor tyrosine kinase PTK6. In: Biochemical and Biophysical Research Communications. 2009 ; Vol. 384, No. 2. pp. 236-242.
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Structural basis of the auto-inhibition mechanism of nonreceptor tyrosine kinase PTK6. / Ko, Sunggeon; Ahn, Kyo Eun; Lee, Young Min; Ahn, Hee Chul; Lee, Weontae.

In: Biochemical and Biophysical Research Communications, Vol. 384, No. 2, 26.06.2009, p. 236-242.

Research output: Contribution to journalArticle

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