title: High-resolution crystal structure of the PDZ1 domain of human protein tyrosine phosphatase PTP-Bas.
abstract: Protein tyrosine phosphatase-Basophil (PTP-Bas) is a membrane-associated protein tyrosine phosphatase with five PDZ domains and is involved in apoptosis, tumorigenesis, and insulin signaling. The interaction between PTP-Bas and tandem-PH-domain-containing protein 1/2 (TAPP1/2) plays an essential role in the regulation of insulin signaling. Despite its high sequence homology with the other PDZ domains, only the PDZ1 domain of PTP-Bas showed distinct binding specificity for TAPP1/2. Although the interaction between PTP-Bas PDZ1 and TAPP1/2 is a therapeutic target for diabetes, the structural basis for the interaction has not been elucidated. In the present study, we determined the crystal structure of the PTP-Bas PDZ1 domain at 1.6 Å resolution. In addition, we calculated the structural models of complexes of PTP-Bas PDZ1 and the C-terminal peptides of TAPP1/2 (referred to as TAPP1p/2p). Structural comparison with the PTP-Bas PDZ2/RA-GEF2 peptide complex revealed a structural basis for distinct binding specificity of PTP-Bas PDZ1 for TAPP1p/2p peptides. Our high-resolution crystal structure of PTP-Bas PDZ1 will serve as a useful template for rational structure-based design of novel anti-diabetes therapeutics.
authors.affiliation: Disease Target Structure Research Center, KRIBB, Daejeon 34141, Republic of Korea; Department of Biological Sciences, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea.
authors.forename: Sang-Ok
authors.initials: SO
authors.lastname: Lee
authors.affiliation: Disease Target Structure Research Center, KRIBB, Daejeon 34141, Republic of Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Lee
authors.affiliation: Disease Target Structure Research Center, KRIBB, Daejeon 34141, Republic of Korea.
authors.forename: Bonsu
authors.initials: B
authors.lastname: Ku
authors.affiliation: Metabolic Regulation Research Center, KRIBB, Daejeon 34141, Republic of Korea.
authors.forename: Kwang-Hee
authors.initials: KH
authors.lastname: Bae
authors.affiliation: Metabolic Regulation Research Center, KRIBB, Daejeon 34141, Republic of Korea.
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea.
authors.forename: Heon M
authors.initials: HM
authors.lastname: Lim
authors.affiliation: Disease Target Structure Research Center, KRIBB, Daejeon 34141, Republic of Korea. Electronic address: ksj@kribb.re.kr.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Disease Target Structure Research Center, KRIBB, Daejeon 34141, Republic of Korea. Electronic address: swchi@kribb.re.kr.
authors.forename: Seung-Wook
authors.initials: SW
authors.lastname: Chi
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000737:chemistry* / Q000378:metabolism*; D040681:Structural Homology, Protein
chemical_list: D010455:Peptides; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13
keywords: Binding specificity; Crystal structure; PDZ domain; Protein tyrosine phosphatase-Basophil; Tandem-PH-domain-containing protein-1