Solid-State NMR Study of Amyloid Nanocrystals and Fibrils Formed by the Peptide GNNQQNY from Yeast Prion Protein Sup35p

详细信息    查看全文

• 作者：Patrick C. A. van der Wel ; Jó ; zef R. Lewandowski ; Robert G. Griffin
• 刊名：Journal of the American Chemical Society
• 出版年：2007
• 出版时间：April 25, 2007
• 年：2007
• 卷：129
• 期：16
• 页码：5117 - 5130
• 全文大小：742K
• 年卷期：v.129,no.16(April 25, 2007)
• ISSN：1520-5126

文摘

Sup35p is a prion protein found in yeast that contains a prion-forming domain characterized bya repetitive sequence rich in Gln, Asn, Tyr, and Gly amino acid residues. The peptide GNNQQNY_7-13 isone of the shortest segments of this domain found to form amyloid fibrils, in a fashion similar to the proteinitself. Upon dissolution in water, GNNQQNY displays a concentration-dependent polymorphism, formingmonoclinic and orthorhombic crystals at low concentrations and amyloid fibrils at higher concentrations.We prepared nanocrystals of both space groups as well as fibril samples that reproducibly contain three(coexisting) structural forms and examined the specimens with magic angle spinning (MAS) solid-statenuclear magnetic resonance. ¹³C and ¹⁵N MAS spectra of both nanocrystals and fibrils reveal narrowresonances indicative of a high level of microscopic sample homogeneity that permitted resonanceassignments of all five species. We observed variations in chemical shift among the three dominant formsof the fibrils which were indicated by the presence of three distinct, self-consistent sets of correlated NMRsignals. Similarly, the monoclinic and orthorhombic crystals exhibit chemical shifts that differ from one anotherand from the fibrils. Collectively, the chemical shift data suggest that the peptide assumes five conformationsin the crystals and fibrils that differ from one another in subtle but distinct ways. This includes variations inthe mobility of the aromatic Tyr ring. The data also suggest that various structures assumed by the peptidemay be correlated to the "steric zipper" observed in the monoclinic crystals.