Probing Protein-Ligand Interactions Involved in Neurodegenerative Diseases Using Native Electrospray Ionization Top-Down Mass Spectrometry

摘要

High-resolution top-down ESI-MS with ECD and CAD was used to determine the ligand binding sites held by non-covalent intereactions. We showed that ECD effectively locates the molecular tweezer binding sites of amyloidogenic proteins α-Synuclein, Aβ-40, and SOD1 at the N-terminal region, K16, and the metal binding loop, respectively. Also ECD and CAD revealed two metal binding motifs near the Nterminus and C-terminus. For α-Synuclein, copper shows a high binding affinity site at residues ~(3)VFMKGLSK10. Cobalt and Manganese share similar motifs around ~A(119)DPDNEAYE~(126) and ~(132)GYQDY~(136) with a lower binding affinity.