Investigation of the copper binding site on the human islet amyloid polypeptide hormone.
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 [hIAPP...Cu (or Al)](n+) and [hIAPP17-30...Cu]2+ complex were investigated by electrospray ionization-mass spectrometry (ESI-MS). The fragmentation patterns of [hIAPP...Cu [or Al)](n+) and [hIAPP17-30...Cu]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 [hIAPP17-30+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.
Department of Applied Chemistry, Kumoh National Institute of Technology, 1 Yangho-Dong, Gumi, Republic of Korea 730-701.
Mi-Ji
MJ
Kim
Ho-Tae
HT
Kim
D000535:Aluminum / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D058225:Plaque, Amyloid / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
D058228:Islet Amyloid Polypeptide; D003300:Copper; D000535:Aluminum