New model for crystalline polyglutamine assemblies and their connection with amyloid fibrils.
Based on the interpretation of X-ray diffraction data reported for crystals of the poly-L-glutamine-rich 19-peptide D(2)Q(15)K(2), Perutz et al. (Proc. Natl. Acad. Sci. USA 2002, 99, 5591-5595) proposed that hollow, water-filled nanotubes are the basic structural motif of amyloid fibers. We are able to offer an alternative interpretation for the same X-ray diffraction data. Our proposed structure consists of beta-sheets, limited in size in the chain direction that stack at an intersheet distance of 0.83 nm to form cross-beta crystallites. The beta-sheets are composed of individual D(2)Q(15)K(2) molecules hydrogen bonding together in the a direction. The relatively linear interchain amide hydrogen bonds in this growth direction occur at two sites: (i) between neighboring backbone amides and (ii) between adjacent (glutamine) side chain amides decorating both surfaces of the beta sheet. The polyQ sub-lattice unit cell is orthorhombic with parameters a =0.950 nm, b = 1.660 nm, and c = 0.695 nm; contains two beta-sheet segments; and has a calculated density of 1.54 g cm(-3). A key ingredient in the proposed structure is the locking of the Q side chains by hydrogen bonding, which allow high-density packing. In addition, there is evidence suggesting that the D(2)Q(15)K(2) molecules adopt a once-folded hairpin conformation.
Sikorski
Pawel
P
Department of Physics, The Norwegian University of Science and Technology, NTNU, NO-7491 Trondheim, Norway. pawel.sikorski@phys.ntnu.no
Atkins
Edward
E
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D014961:X-Ray Diffraction
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010455:Peptides; C097188:polyglutamine