Investigation of the Copper Binding Site on the Human Islet Amyloid Polypeptide Hormone

Abstract

The metal ion binding sites of human islet amyloid polypeptide (hIAPP) have been investigated to explain the biological activity difference in the fibril formation process. The structures of [hIAPPṫCu (or Al)]ⁿ⁺ and [hIAPP_17–30ṫCu]²⁺ complex were investigated by electrospray ionization–mass spectrometry (ESI-MS). The fragmentation patterns of [hIAPPṫCu (or Al)]ⁿ⁺ and [hIAPP_17–30ṫCu]²⁺ complex were analyzed by tandem mass spectrometry (MS/MS) and multi-stage mass spectrometry (MS³) spectra. The [hIAPP+Cu+H]³⁺, [hIAPP+Al+H]⁴⁺ and [hIAPP_17–30+Cu]²⁺ complexes were observed in MS spectra. The Cu binding site of hIAPP is suggested to be the N₂₂–F–G–A–I₂₆ part for the [hIAPP+Cu+H]³⁺ gas-phase complex. The original hIAPP conformation was supposed to be changed by the interaction between the Cu ion and the N₂₂–F–G–A–I₂₆ part in the [hIAPP+Cu+H]³⁺ gas-phase complex.