High affinity copper binding by stefin B (cystatin B) and its role in the inhibition of amyloid fibrillation.

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Zerovnik E, Skerget K, Tusek-Znidaric M, Loeschner C, Brazier MW, Brown DR

High affinity copper binding by stefin B (cystatin B) and its role in the inhibition of amyloid fibrillation.

FEBS J. 2006 Sep;273(18):4250-63.

PubMed ID

16939620 [ View in PubMed

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Abstract

We show that human stefin B, a protease inhibitor from the family of cystatins, is a copper binding protein, unlike stefin A. We have used isothermal titration calorimetry to directly monitor the binding event at pH 7 and pH 5. At pH 7 stefin B shows a picomolar affinity for copper but at pH 5 the affinity is in the nanomolar range. There is no difference in the affinity of copper between the wildtype stefin B (E31 isoform) and a variant (Y31 isoform), whereas the mutant (P79S), which is tetrameric, does not bind copper. The conformation of stefin B remains unaltered by copper binding. It is known that below pH 5 stefin B undergoes a conformational change and amyloid fibril formation. We show that copper binding inhibits the amyloid fibril formation and, to a lesser degree, the initial aggregation. Similarities to and differences from other copper binding amyloidogenic proteins are discussed.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cupric Chloride	Cystatin-B	Protein	Humans	Unknown	Not Available	Details