Journal article

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

Geoffrey K-W Kong, Julian J Adams, Hugh H Harris, John F Boas, Cyril C Curtain, Denise Galatis, Colin L Masters, Kevin J Barnham, William J McKinstry, Roberto Cappai, Michael W Parker

JOURNAL OF MOLECULAR BIOLOGY | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD | Published : 2007

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 ..

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