The role of metals in protein conformational disorders - The case of prion protein and Aβ -peptide

6th Young Researcher Meeting, L'Aquila 2015

De Santis, E.^1 ; Minicozzi, V.^1 ; Morante, S.^1 ; Rossi, G.C.^1,2 ; Stellato, F.^1

Dipartimento di Fisica, Università di Roma Tor Vergata, INFN Sezione di Roma Tor Vergata, Via della Ricerca Scientifica, Roma

00133, Italy^1

Centro Fermi, Piazza del Viminale, Roma

00184, Italy^2

关键词: Amyloid-beta peptides;    Amyloidogenic proteins;    Chemical selectivity;    Conformational disorders;    Copper and zinc ions;    Physiological condition;    Structural characterization;    Transmissible spongiform encephalopathies;   

Others  :  https://iopscience.iop.org/article/10.1088/1742-6596/689/1/012028/pdf
DOI  :  10.1088/1742-6596/689/1/012028

来源: IOP

【 摘 要 】

Protein conformational disorders are members of a vast class of pathologies in which endogenous proteins or peptides undergo a misfolding process by switching from the physiological soluble configuration to a pathological fibrillar insoluble state. An important, but not yet fully elucidated, role in the process appears to be played by transition metal ions, mainly copper and zinc. X-ray absorption spectroscopy is one of the most suitable techniques for the structural characterization of biological molecules in complex with metal. Owing to its chemical selectivity and sensitivity to the local atomic geometry around the absorber, it can be successfully used to study the environment of metal ions in complex with proteins and peptides in physiological conditions. In this paper we present X-ray absorption spectroscopy studies of the metal ions coordination modes in systems where metals are complexed with specific amyloidogenic proteins and peptides. In particular, we show results concerning the Amyloid β peptide, that is involved in Alzheimer's disease, and the Prion protein, that is responsible for the Transmissible Spongiform Encephalopathy. Our findings suggest that the copper and zinc ions may play a crucial role in the aggregation and fibril formation process of these two biomolecules. Elucidating this kind of interaction could be a key preliminary step before any viable therapy can be conceived or designed.