title: Structural Basis for Interactions Between Contactin Family Members and Protein-tyrosine Phosphatase Receptor Type G in Neural Tissues.
abstract: Protein-tyrosine phosphatase receptor type G (RPTPγ/PTPRG) interacts in vitro with contactin-3-6 (CNTN3-6), a group of glycophosphatidylinositol-anchored cell adhesion molecules involved in the wiring of the nervous system. In addition to PTPRG, CNTNs associate with multiple transmembrane proteins and signal inside the cell via cis-binding partners to alleviate the absence of an intracellular region. Here, we use comprehensive biochemical and structural analyses to demonstrate that PTPRG·CNTN3-6 complexes share similar binding affinities and a conserved arrangement. Furthermore, as a first step to identifying PTPRG·CNTN complexes in vivo, we found that PTPRG and CNTN3 associate in the outer segments of mouse rod photoreceptor cells. In particular, PTPRG and CNTN3 form cis-complexes at the surface of photoreceptors yet interact in trans when expressed on the surfaces of apposing cells. Further structural analyses suggest that all CNTN ectodomains adopt a bent conformation and might lie parallel to the cell surface to accommodate these cis and trans binding modes. Taken together, these studies identify a PTPRG·CNTN complex in vivo and provide novel insights into PTPRG- and CNTN-mediated signaling.
authors.affiliation: From the Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri 64110.
authors.forename: Roman M
authors.initials: RM
authors.lastname: Nikolaienko
authors.affiliation: the Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720.
authors.forename: Michal
authors.initials: M
authors.lastname: Hammel
authors.affiliation: the Départment de Neuroscience, Institut Pasteur de Paris, 25-28 Rue du Dr. Roux, 75624 Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Epigenetics and Cell Fate, UMR 7216, CNRS, Paris, France, and.
authors.forename: Véronique
authors.initials: V
authors.lastname: Dubreuil
authors.affiliation: From the Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri 64110.
authors.forename: Rana
authors.initials: R
authors.lastname: Zalmai
authors.affiliation: From the Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri 64110.
authors.forename: David R
authors.initials: DR
authors.lastname: Hall
authors.affiliation: From the Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri 64110.
authors.forename: Nurjahan
authors.initials: N
authors.lastname: Mehzabeen
authors.affiliation: From the Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri 64110.
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Karuppan
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Epigenetics and Cell Fate, UMR 7216, CNRS, Paris, France, and.
authors.forename: Sheila
authors.initials: S
authors.lastname: Harroch
authors.affiliation: the Department of Basic Medical Science, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri 64108.
authors.forename: Salvatore L
authors.initials: SL
authors.lastname: Stella
authors.affiliation: From the Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri 64110, bouyains@umkc.edu.
authors.forename: Samuel
authors.initials: S
authors.lastname: Bouyain
mesh_terms: D000818:Animals; D058966:Contactins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009417:Nerve Tissue / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D058966:Contactins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; C516851:Ptprg protein, mouse; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
keywords: cell adhesion; cell surface; contactin; crystal structure; immunoglobulin|L-like domain; protein phosphatase; retina