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Crystal structure of the extracellular juxtamembrane region of Robo1.
Barak, Reut; Lahmi, Roxane; Gevorkyan-Airapetov, Lada; Levy, Eliad; Tzur, Amit; Opatowsky, Yarden.
Afiliación
  • Barak R; The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
  • Lahmi R; The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel; Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 5290002, Israel.
  • Gevorkyan-Airapetov L; The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
  • Levy E; The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
  • Tzur A; The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel; Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 5290002, Israel.
  • Opatowsky Y; The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel. Electronic address: yarden.opatowsky@biu.ac.il.
J Struct Biol ; 186(2): 283-91, 2014 May.
Article en En | MEDLINE | ID: mdl-24607414
Robo receptors play pivotal roles in neurodevelopment, and their deregulation is implicated in several neuropathological conditions and cancers. To date, the mechanism of Robo activation and regulation remains obscure. Here we present the crystal structure of the juxtamembrane (JM) domains of human Robo1. The structure exhibits unexpectedly high backbone similarity to the netrin and RGM binding region of neogenin and DCC, which are functionally related receptors of Robo1. Comparison of these structures reveals a conserved surface that overlaps with a cluster of oncogenic and neuropathological mutations found in all Robo isoforms. The structure also reveals the intricate folding of the JM linker, which points to its role in Robo1 activation. Further experiments with cultured cells demonstrate that exposure or relief of the folded JM linker results in enhanced shedding of the Robo1 ectodomain.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Inmunológicos / Modelos Moleculares / Proteínas del Tejido Nervioso Límite: Humans Idioma: En Revista: J Struct Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2014 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Inmunológicos / Modelos Moleculares / Proteínas del Tejido Nervioso Límite: Humans Idioma: En Revista: J Struct Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2014 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos