title: Structural basis for the dephosphorylating activity of PTPRQ towards phosphatidylinositide substrates.
abstract: Unlike other classical protein tyrosine phosphatases (PTPs), PTPRQ (PTP receptor type Q) has dephosphorylating activity towards phosphatidylinositide (PI) substrates. Here, the structure of the catalytic domain of PTPRQ was solved at 1.56 Å resolution. Overall, PTPRQ adopts a tertiary fold typical of other classical PTPs. However, the disordered M6 loop of PTPRQ surrounding the catalytic core and the concomitant absence of interactions of this loop with residues in the PTP loop results in a flat active-site pocket. On the basis of structural and biochemical analyses, it is proposed that this structural feature might facilitate the accommodation of large substrates, making it suitable for the dephosphorylation of PI substrates. Moreover, subsequent kinetic experiments showed that PTPRQ has a strong preferences for PI(3,4,5)P3 over other PI substrates, suggesting that its regulation of cell survival and proliferation reflects downregulation of Akt signalling.
authors.affiliation: Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 111 Gwahangno, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Keum Ran
authors.initials: KR
authors.lastname: Yu
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Kim
authors.forename: Suk-Kyeong
authors.initials: SK
authors.lastname: Jung
authors.forename: Bonsu
authors.initials: B
authors.lastname: Ku
authors.forename: Hwangseo
authors.initials: H
authors.lastname: Park
authors.forename: Sa Yeon
authors.initials: SY
authors.lastname: Cho
authors.forename: Hyeyun
authors.initials: H
authors.lastname: Jung
authors.forename: Sang J
authors.initials: SJ
authors.lastname: Chung
authors.forename: Kwang Hee
authors.initials: KH
authors.lastname: Bae
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Lee
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Erikson
authors.forename: Seong Eon
authors.initials: SE
authors.lastname: Ryu
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D018129:Phosphatidylinositol Phosphates; C060974:phosphatidylinositol 3,4,5-triphosphate; C516917:PTPRQ protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3
keywords: PTP receptor type Q; protein tyrosine phosphatases