Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Structural and Biochemical Characterization of the Two Drosophila Low Molecular Weight-Protein Tyrosine Phosphatases DARP and Primo-1

  • Lee, Hye Seon (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Mo, Yeajin (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Shin, Ho-Chul (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Seung Jun (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Ku, Bonsu (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2020.09.22
  • Accepted : 2020.11.19
  • Published : 2020.12.31
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Abstract

The Drosophila genome contains four low molecular weight-protein tyrosine phosphatase (LMW-PTP) members: Primo-1, Primo-2, CG14297, and CG31469. The lack of intensive biochemical analysis has limited our understanding of these proteins. Primo-1 and CG31469 were previously classified as pseudophosphatases, but CG31469 was also suggested to be a putative protein arginine phosphatase. Herein, we present the crystal structures of CG31469 and Primo-1, which are the first Drosophila LMW-PTP structures. Structural analysis showed that the two proteins adopt the typical LMW-PTP fold and have a canonically arranged P-loop. Intriguingly, while Primo-1 is presumed to be a canonical LMW-PTP, CG31469 is unique as it contains a threonine residue at the fifth position of the P-loop motif instead of highly conserved isoleucine and a characteristically narrow active site pocket, which should facilitate the accommodation of phosphoarginine. Subsequent biochemical analysis revealed that Primo-1 and CG31469 are enzymatically active on phosphotyrosine and phosphoarginine, respectively, refuting their classification as pseudophosphatases. Collectively, we provide structural and biochemical data on two Drosophila proteins: Primo-1, the canonical LMW-PTP protein, and CG31469, the first investigated eukaryotic protein arginine phosphatase. We named CG31469 as DARP, which stands for Drosophila ARginine Phosphatase.

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References

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