Rational design of amyloid-based materials requires structural insights into such materials.Here,we explore to use side-chain-based infrared(IR)probe technique to elucidate the structural details of an amyloid nanosheet by A?(16-22)variant,KLVXFAK,where X is p-cyanophenylalanine with its side-chain cyano group being the IR probe.Using side-chain-based IR probe technique to obtain the structural constraints at both secondary and quaternary structural levels,we propose a hierarchical structural model for the KLVXFAK nanosheet.The nanosheet can be viewed as a stack of class 7 type steric-zipper-like amyloid structures with a unique out-of-register inter-sheet arrangement: the ?-sheets are stacked along zippering axis with each individual ?-sheet sheared relative to each other through the cyano-lysine hydrogen bond.With such configuration,the side view of the nanosheet is similar to that of a stack of tilted-aligned roof tiles with the ?-sheet being the tile.This model can nicely interpret both the IR spectroscopic data and the atomic force microscopy height data.To our knowledge,this work provides the first example of using side-chain-based IR probe technique to building a structural model for amyloid-based materials. |