NR AAXK
AU Balbirnie,M.; Grothe,R.; Eisenberg,D.S.
TI An amyloid-forming peptide from the yeast prion Sup35 reveals a dehydrated beta-sheet structure for amyloid
QU Proceedings of the National Academy of Sciences of the United States of America 2001 Feb 27; 98(5): 2375-80
IA http://www.pnas.org/cgi/content/full/98/5/2375
PT journal article
AB X-ray diffraction and other biophysical tools reveal features of the atomic structure of an amyloid-like crystal. Sup35, a prion-like protein in yeast, forms fibrillar amyloid assemblies intrinsic to its prion function. We have identified a polar peptide from the N-terminal prion-determining domain of Sup35 that exhibits the amyloid properties of full-length Sup35, including cooperative kinetics of aggregation, fibril formation, binding of the dye Congo red, and the characteristic cross-beta x-ray diffraction pattern. Microcrystals of this peptide also share the principal properties of the fibrillar amyloid, including a highly stable, beta-sheet-rich structure and the binding of Congo red. The x-ray powder pattern of the microcrystals, extending to 0.9-A resolution, yields the unit cell dimensions of the well-ordered structure. These dimensions restrict possible atomic models of this amyloid-like structure and demonstrate that it forms packed, parallel-stranded beta-sheets. The unusually high density of the crystals shows that the packed beta-sheets are dehydrated, despite the polar character of the side chains. These results suggest that amyloid is a highly intermolecularly bonded, dehydrated array of densely packed beta-sheets. This dry beta-sheet could form as Sup35 partially unfolds to expose the peptide, permitting it to hydrogen-bond to the same peptide of other Sup35 molecules. The implication is that amyloid-forming units may be short segments of proteins, exposed for interactions by partial unfolding.
MH Amino Acid Sequence; Amyloid/*chemistry; Base Sequence; Crystallization; Crystallography, X-Ray; DNA Primers; Fungal Proteins/*chemistry; Microscopy, Electron; Prions/*chemistry; Protein Conformation; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.; *Saccharomyces cerevisiae Proteins; Spectroscopy, Fourier Transform Infrared
AD University of California-Department of Energy Laboratory of Structural Biology and Molecular Medicine, Department of Chemistry and Biochemistry, Box 951570, University of California, Los Angeles, CA 90095-1570, USA
SP englisch
PO USA