Nucleobase-directed amyloid nanotube assembly.
Cytosine nucleobases were successfully incorporated into the side chain of the self-assembling amyloid peptide fragment HHQALVFFA to give ccAQLVFFA. At a pH range of 3-4, where cytosine is expected to be partially protonated, small-angle X-ray scattering analyses revealed the nucleobase peptide assembles to be well-defined nanotubes with an outer diameter of 24.8 nm and wall thicknesses of 3.3 nm. FT-IR and X-ray diffraction confirmed beta-sheet-rich assembly with the characteristic cross-beta architecture of amyloid. The beta-sheet registry, determined by measuring (13)CO-(13)CO backbone distances with solid-state NMR and linear dichroism, placed the cytosine bases roughly perpendicular to the nanotube axis, resulting in a model where the complementary interactions between the cytosine bases increases beta-sheet stacking to give the nanotube architecture. These scaffolds then extend the templates used to encode biological information beyond the nucleic acid duplexes and into covalent networks whose self-assembly is still defined by a precise complementarity of the side-chain registry.
Liu
Peng
P
Center for Fundamental and Applied Molecular Evolution, Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA.
Ni
Rong
R
Mehta
Anil K
AK
Childers
W Seth
WS
Lakdawala
Ami
A
Pingali
Sai Venkatesh
SV
Thiyagarajan
Pappannan
P
Lynn
David G
DG
D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D003198:Computer Simulation; D006860:Hydrogen Bonding; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D008968:Molecular Conformation; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D013057:Spectrum Analysis
D000682:Amyloid