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

Citations Over TimeTop 1% of 2007 papers

Abstract

Sup35p is a prion protein found in yeast that contains a prion-forming domain characterized by a repetitive sequence rich in Gln, Asn, Tyr, and Gly amino acid residues. The peptide GNNQQNY7-13 is one of the shortest segments of this domain found to form amyloid fibrils, in a fashion similar to the protein itself. Upon dissolution in water, GNNQQNY displays a concentration-dependent polymorphism, forming monoclinic 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-state nuclear magnetic resonance. 13C and 15N MAS spectra of both nanocrystals and fibrils reveal narrow resonances indicative of a high level of microscopic sample homogeneity that permitted resonance assignments of all five species. We observed variations in chemical shift among the three dominant forms of the fibrils which were indicated by the presence of three distinct, self-consistent sets of correlated NMR signals. Similarly, the monoclinic and orthorhombic crystals exhibit chemical shifts that differ from one another and from the fibrils. Collectively, the chemical shift data suggest that the peptide assumes five conformations in the crystals and fibrils that differ from one another in subtle but distinct ways. This includes variations in the mobility of the aromatic Tyr ring. The data also suggest that various structures assumed by the peptide may be correlated to the "steric zipper" observed in the monoclinic crystals.

Related Papers

• → Orthorhombic phases in bulk pure HfO2: Experimental observation from perturbed angular correlation spectroscopy(2020)13 cited
• → Induction of AApoAII amyloidosis by various heterogeneous amyloid fibrils(2004)43 cited
• → 13C and 1H NMR chemical shifts of 9‐alkyltriptycenes. Linear variations of 13C chemical shifts on successive substitution of the 9‐methyl hydrogen atoms by methyl groups(1987)
• Microwave Synthesis and Characterization of Both Cubic and Orthorhombic ZrW_(0.8)Mo_(1.2)O_8(2004)
• → Synthesis and Crystal Structure of a New Orthorhombic Polytype of Potassium Ferricyanide(2022)