NR ASQO
AU Nelson,R.; Sawaya,M.R.; Balbirnie,M.; Madsen,A.O.; Riekel,C.; Grothe,R.; Eisenberg,D.
TI Structure of the cross-beta spine of amyloid-like fibrils
QU Nature 2005 Jun 9; 435(7043): 773-8
KI Nature. 2005 Jun 9;435(7043):747-9. PMID: 15944684
PT journal article
AB Numerous soluble proteins convert to insoluble amyloid-like fibrils that have common properties. Amyloid fibrils are associated with fatal diseases such as Alzheimer's, and amyloid-like fibrils can be formed in vitro. For the yeast protein Sup35, conversion to amyloid-like fibrils is associated with a transmissible infection akin to that caused by mammalian prions. A seven-residue peptide segment from Sup35 forms amyloid-like fibrils and closely related microcrystals, from which we have determined the atomic structure of the cross-beta spine. It is a double beta-sheet, with each sheet formed from parallel segments stacked in register. Side chains protruding from the two sheets form a dry, tightly self-complementing steric zipper, bonding the sheets. Within each sheet, every segment is bound to its two neighbouring segments through stacks of both backbone and side-chain hydrogen bonds. The structure illuminates the stability of amyloid fibrils, their self-seeding characteristic and their tendency to form polymorphic structures.
MH Amides/chemistry; Amino Acid Sequence; Amyloid/*chemistry/metabolism; Crystallization; Crystallography, X-Ray; Hydrogen Bonding; *Models, Molecular; Molecular Sequence Data; Peptide Fragments/*chemistry/metabolism; Prions/*chemistry/metabolism; Protein Structure, Secondary; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.; Saccharomyces cerevisiae/*chemistry; Saccharomyces cerevisiae Proteins/*chemistry/metabolism; Thermodynamics
AD Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, Box 951570, UCLA, Los Angeles, California 90095-1570, USA
SP englisch
PO England