2fkl Citations

Structural studies of the Alzheimer's amyloid precursor protein copper-binding domain reveal how it binds copper ions.

J Mol Biol 367 148-61 (2007)
Related entries: 2fjz, 2fk1, 2fk2, 2fk3

Cited: 52 times
EuropePMC logo PMID: 17239395

Abstract

Alzheimer's disease (AD) is the major cause of dementia. Amyloid beta peptide (Abeta), generated by proteolytic cleavage of the amyloid precursor protein (APP), is central to AD pathogenesis. APP can function as a metalloprotein and modulate copper (Cu) transport, presumably via its extracellular Cu-binding domain (CuBD). Cu binding to the CuBD reduces Abeta levels, suggesting that a Cu mimetic may have therapeutic potential. We describe here the atomic structures of apo CuBD from three crystal forms and found they have identical Cu-binding sites despite the different crystal lattices. The structure of Cu(2+)-bound CuBD reveals that the metal ligands are His147, His151, Tyr168 and two water molecules, which are arranged in a square pyramidal geometry. The site resembles a Type 2 non-blue Cu center and is supported by electron paramagnetic resonance and extended X-ray absorption fine structure studies. A previous study suggested that Met170 might be a ligand but we suggest that this residue plays a critical role as an electron donor in CuBDs ability to reduce Cu ions. The structure of Cu(+)-bound CuBD is almost identical to the Cu(2+)-bound structure except for the loss of one of the water ligands. The geometry of the site is unfavorable for Cu(+), thus providing a mechanism by which CuBD could readily transfer Cu ions to other proteins.

Reviews - 2fkl mentioned but not cited (3)

  1. Nanotechnology, nanotoxicology, and neuroscience. Suh WH, Suslick KS, Stucky GD, Suh YH. Prog Neurobiol 87 133-170 (2009)
  2. Copper binding to the Alzheimer's disease amyloid precursor protein. Kong GK, Miles LA, Crespi GA, Morton CJ, Ng HL, Barnham KJ, McKinstry WJ, Cappai R, Parker MW. Eur Biophys J 37 269-279 (2008)
  3. Alzheimer's disease--a panorama glimpse. Zhao LN, Lu L, Chew LY, Mu Y. Int J Mol Sci 15 12631-12650 (2014)

Articles - 2fkl mentioned but not cited (3)



Reviews citing this publication (18)

  1. Metals in Alzheimer's and Parkinson's diseases. Barnham KJ, Bush AI. Curr Opin Chem Biol 12 222-228 (2008)
  2. Metal dyshomeostasis and oxidative stress in Alzheimer's disease. Greenough MA, Camakaris J, Bush AI. Neurochem Int 62 540-555 (2013)
  3. Copper in the brain and Alzheimer's disease. Hung YH, Bush AI, Cherny RA. J Biol Inorg Chem 15 61-76 (2010)
  4. Structure and functions of the human amyloid precursor protein: the whole is more than the sum of its parts. Gralle M, Ferreira ST. Prog Neurobiol 82 11-32 (2007)
  5. How is protein aggregation in amyloidogenic diseases modulated by biological membranes? Aisenbrey C, Borowik T, Byström R, Bokvist M, Lindström F, Misiak H, Sani MA, Gröbner G. Eur Biophys J 37 247-255 (2008)
  6. The genes associated with early-onset Alzheimer's disease. Dai MH, Zheng H, Zeng LD, Zhang Y. Oncotarget 9 15132-15143 (2018)
  7. Werner coordination chemistry and neurodegeneration. Telpoukhovskaia MA, Orvig C. Chem Soc Rev 42 1836-1846 (2013)
  8. Wilson disease: not just a copper disorder. Analysis of a Wilson disease model demonstrates the link between copper and lipid metabolism. Huster D, Lutsenko S. Mol Biosyst 3 816-824 (2007)
  9. Polyphenols as Potential Metal Chelation Compounds Against Alzheimer's Disease. Lakey-Beitia J, Burillo AM, La Penna G, Hegde ML, Rao KS. J Alzheimers Dis 82 S335-S357 (2021)
  10. Brain proteins that mind metals: a neurodegenerative perspective. Brown DR. Dalton Trans 4069-4076 (2009)
  11. Novel drug targets based on metallobiology of Alzheimer's disease. Bandyopadhyay S, Huang X, Lahiri DK, Rogers JT. Expert Opin Ther Targets 14 1177-1197 (2010)
  12. Plant polyphenols in the treatment of age-associated diseases: revealing the pleiotropic effects of icariin by network analysis. Schluesener JK, Schluesener H. Mol Nutr Food Res 58 49-60 (2014)
  13. Structure and Synaptic Function of Metal Binding to the Amyloid Precursor Protein and its Proteolytic Fragments. Wild K, August A, Pietrzik CU, Kins S. Front Mol Neurosci 10 21 (2017)
  14. Biological X-ray absorption spectroscopy (BioXAS): a valuable tool for the study of trace elements in the life sciences. Strange RW, Feiters MC. Curr Opin Struct Biol 18 609-616 (2008)
  15. Regulation of the alternative β-secretase meprin β by ADAM-mediated shedding. Scharfenberg F, Armbrust F, Marengo L, Pietrzik C, Becker-Pauly C. Cell Mol Life Sci 76 3193-3206 (2019)
  16. Membrane topology of gp41 and amyloid precursor protein: interfering transmembrane interactions as potential targets for HIV and Alzheimer treatment. Abad C, Martínez-Gil L, Tamborero S, Mingarro I. Biochim Biophys Acta 1788 2132-2141 (2009)
  17. Structural biology of cell surface receptors implicated in Alzheimer's disease. Hermans SJ, Nero TL, Morton CJ, Gooi JH, Crespi GAN, Hancock NC, Gao C, Ishii K, Markulić J, Parker MW. Biophys Rev 14 233-255 (2022)
  18. Applications of electron paramagnetic resonance to studies of neurological disease. Boas JF, Drew SC, Curtain CC. Eur Biophys J 37 281-294 (2008)

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