1H-, 13C- and 15N-NMR assignment of the N-terminal domain of human cerebral dopamine neurotrophic factor (CDNF)

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• 作者：Cristiane Latgé (1)
  Kátia M. S. Cabral (1)
  Marcius S. Almeida (1)
  Débora Foguel (1)
  
• 关键词：Neurotrophic factor ; NMR chemical shift ; Armet ; like protein 1 ; Parkinson’s Disease
• 刊名：Biomolecular NMR Assignments
• 出版年：2013
• 出版时间：April 2013
• 年：2013
• 卷：7
• 期：1
• 页码：101-103
• 全文大小：536KB
• 参考文献：1. Bax A, Grzesiek S (1993) Methodological advances in protein NMR. Acc Chem Res 26:131-38 CrossRef
  2. Dauer W (2007) Neurotrophic factors and Parkinson’s disease: the emergence of a New player? Sci STKE 411:pe60
  3. Lindholm P, Voutilainen MH, Laurén J, Per?nen J, Lepp?nen VM, Andressoo JO, Lindahl M, Janhunen S, Kalkkinen N, Timmusk T, Tuominen RK, Saarma M (2007) Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo. Nature 448:73-7 CrossRef
  4. Parkash V, Lindholm P, Per?nen J, Kalkkinen N, Oksanen E, Saarma M, Lepp?nen VM, Goldman A (2009) The structure of the conserved neurotrophic factors MANF and CDNF explains why they are bifunctional. Protein Eng Des Sel 4:233-41 CrossRef
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  6. Wishart DS, Sykes BD (1994) The 13C chemical shift index. A simple method for the identification of protein secondary structure using 13C chemical shift data. J Biomol NMR 4:171-80 CrossRef
  
• 作者单位：Cristiane Latgé (1)
  Kátia M. S. Cabral (1)
  Marcius S. Almeida (1)
  Débora Foguel (1)
  
  1. Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
  
• ISSN：1874-270X

文摘

Parkinson’s disease (PD) is a neurodegenerative disorder that is caused by the death of midbrain dopaminergic neurons. Current therapies for PD do not halt the neurodegeneration nor repair the affected neurons. Therefore, search for novel neurotrophic factors (NTF) for midbrain dopaminergic neurons, which could be used in novel therapeutic approaches, is highly wanted. In 2007, a potent NTF for dopaminergic neurons was described as the conserved dopamine neurotrophic factor (CDNF). Single doses of this protein protect and restore dopaminergic neurons in experimental models of PD. CDNF has two domains; an N-terminal saposin-like domain, which may bind to membranes; and a presumably intrinsically unstructured C-terminal which contains an internal cysteine bridge in a CXXC motif similar to that of thiol/disulphide oxidoreductases and isomerases, and may thus reduce the endoplasmic reticulum stress caused by incorrectly folded proteins. We show for the first time the nuclear magnetic resonance assignment of N-terminal domain of recombinant CDNF (residues 1-05) by solution 2D and 3D NMR spectroscopy. We were able to obtain a nearly complete resonance assignment, which is the first step toward the solution structure determination of this neurotrophic factor.