About: Characterization of MAGE proteins: cofactors for E3 ubiquitin ligases?     Goto   Sponge   NotDistinct   Permalink

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  • Lidské buňky jsou schopné exprimovat 35 různých MAGE (Melanoma antigen) proteinů. MAGEG1-Nse1 heterodimer je součástí Smc5-6 komplexu, který se účastní opravy poškozené DNA. Kromě Nse1, který obsahuje RING-finger E3 ubiquitin ligasovou doménu, existují další dva příklady MAGE-RING finger interakcí. Pokus o predikci struktury MAGE homologní domény (MHD) naznačil její částečnou podobnost s doménou molekuly cullinu, který tvoří E3 ubiquitin ligasový komplex. V tomto projektu chceme ověřit hypotézu: %22MAGE proteiny slouží jako kofaktory E3 RING ubiquitin ligás.%22 Budeme mutovat konzervované aminokyselinové zbytky MAGEG1 proteinu tak, abychom zjistili, které z nich se podílí na interakci s Nse1. U specifických mutant budeme sledovat schopnost komplexu Smc5-6 učastnit se opravy DNA. Najdeme další RING finger proteiny a podrobíme je podobné analýze s cílem charakterizovat obecné interakční vlastnosti MAGE proteinů. Strukturu MHD budeme studovat pomocí NMR spektroskopie a difrakce krystalů.
  • The MAGE (Melanoma antigen) family consists of 35 proteins in humans that contain a %22MAGE homology domain%22 (MHD) but have widely differing functions. The Smc5-6 complex, which functions in DNA repair, consists of MAGEG1-Nse1 heterodimer. Taking, Nse1 is a putative RING finger E3 ubiquitin ligase, there are two other reports of MAGE proteins interacting with RING-finger proteins. In addition, our structure predictions suggest that part of MHD has similarities to cullin components of E3 ligases. We will test the hypothesis that MAGE proteins are cofactors in E3 ligase complexes. We will carry out structural analyses of the MHD fold using NMR spectroscopy and X-ray crystallography to test our structural predictions. We will mutate critical residues in MAGEG1, that we predict to interact with Nse1, to see if this specifically destroys this interaction and affects DNA repair. We will search for and analyze new RING partners interacting with MAGE proteins to find out MHD common features. (en)
Title
  • Characterization of MAGE proteins: cofactors for E3 ubiquitin ligases? (en)
  • Charakterizace MAGE proteinů: kofaktory E3 ubiquitin ligáz?
skos:notation
  • IAA501630902
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  • MAGE (melanoma antigen) proteins; protein structure and interactions; RING finger proteins; E3 ubiquitin ligases; DNA repair; chromatin structure; SMC5-6 complex (en)
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  • Objeven evolučně konzervovaný hydrofobní žlábek na povrchu proteinů Nse3/MAGE zodpovědný za interakci s doménou konzervovanou v proteinech Nse4/EID. Identifikovány a charakterizovány nové interakce mezi MAGE a proteiny obsahujícími RING-finger domény. (cs)
  • A conserved hydrophobic pocket was discovered on the surface of the Nse3/MAGE proteins. The Nse4/EID domain binding to the Nse3/MAGE pocket was described. New interactions between the MAGE and RING-finger proteins were identified and characterized. (en)
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  • DNA repair
  • E3 ubiquitin ligases
  • RING finger proteins
  • chromatin structure
  • protein structure and interactions
  • MAGE (melanoma antigen) proteins
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