A NOVEL ZINC(II) BINDING-SITE MODULATES THE FUNCTION OF THE BETA-A4 AMYLOID PROTEIN-PRECURSOR OF ALZHEIMERS-DISEASE

被引:0
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作者
BUSH, AI
MULTHAUP, G
MOIR, RD
WILLIAMSON, TG
SMALL, DH
RUMBLE, B
POLLWEIN, P
BEYREUTHER, K
MASTERS, CL
机构
[1] UNIV MELBOURNE, DEPT PATHOL, PARKVILLE, VIC 3052, AUSTRALIA
[2] MENTAL HLTH RES INST VICTORIA, NEUROPATHOL LAB, PARKVILLE, VIC 3052, AUSTRALIA
[3] UNIV HEIDELBERG, CTR MOLEC BIOL, W-6900 HEIDELBERG, GERMANY
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中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Abnormalities of zinc metabolism occur in Alzheimer's disease (AD), a condition where pathological catabolism of the amyloid protein precursor (APP) causes cerebral betaA4 amyloidosis. An association between zinc and ApP metabolism was sought by studying the binding of Zn-65(2+) to APP. Zn-65(2+) bound in a rapid, saturable, and specific manner (K(D) = 764 nM). A novel zinc binding motif, strongly conserved between members of the APP family, was located between the cysteine-rich and negatively charged domains of the protein. Zinc increased binding of ''P to heparin and has been shown to potentiate the inhibition of coagulation factor XIa by an APP isoform containing a Kunitz-type inhibitory domain (Komiyama, Y., Murakami, T., Egawa, H., Okubo, S., Yasunaga, K., and Murata, K. (1992) Thromb. Res. 66,397-408) situated near the zinc binding region. Zinc is a factor that modulates the functional properties of the substrate for betaA4 amyloidogenesis.
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页码:16109 / 16112
页数:4
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