Molecular organization of amyloid protofilament-like assembly of betabellin 15D: helical array of beta-sandwiches.
Betabellin is a 32-residue peptide engineered to fold into a four-stranded antiparallel beta-sheet protein. Upon air oxidation, the betabellin peptides can fold and assemble into a disulfide-bridged homodimer, or beta-sandwich, of 64 residues. Recent biophysical and ultrastructural studies indicate that betabellin 15D (B15D) (a homodimer of HSLTAKIpkLTFSIAphTYTCAVpkYTAKVSH, where p = DPro, k = DLys, and h = DHis) forms unbranched, 35-A wide assemblies that resemble the protofilaments of amyloid fibers. In the present study, we have analyzed in detail the X-ray diffraction patterns of B15D prepared from acetonitrile. The fiber diffraction analysis indicated that the B15D fibril was composed of a double helix defined by the selection rule l = n + 7m (where l is even, and n and m are any integers), and having a 199-A period and pitch, 28-A rise per unit, and 10-A radius. This helical model is equivalent to a reverse-handed, single helix with half the period and defined by the selection rule l = -3n + 7m (where l is any integer). The asymmetric unit is the single B15D beta-sandwich molecule. These results suggest that the betabellin assembly that models the protofilaments of amyloid fibers is made up of discrete subunits on a helical array. Multiple intersheet hydrogen bonds in the axial direction and intersandwich polar interactions in the lateral direction stabilize the array.
Inouye
Hideyo
H
Biology Department, Boston College, Chestnut Hill, Massachusetts 02467-3811, USA. inouyeh@bc.edu
Bond
Jeremy E
JE
Deverin
Sean P
SP
Lim
Amareth
A
Costello
Catherine E
CE
Kirschner
Daniel A
DA
D000097:Acetonitriles / Q000494:pharmacology; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D055592:Biophysical Phenomena; D001703:Biophysics; D019281:Dimerization; D008958:Models, Molecular; D015233:Models, Statistical; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D014176:Protein Biosynthesis; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D011994:Recombinant Proteins; D012542:Scattering, Radiation; D014961:X-Ray Diffraction
D000097:Acetonitriles; D000682:Amyloid; D010455:Peptides; D011506:Proteins; D011994:Recombinant Proteins; C114709:betabellin 15; C032159:acetonitrile