Two 'protein folding codes' can be inferred from empirical classifications using Tlusty's topological approach

Abstract

AbstractTlusty's topological arguments regarding the genetic code are applied to the classification of tertiary irregular protein symmetries. Unlike the genetic case, two protein folding codes are found, a 'normal' globular and a 'pathological' amyloid version. The underlying normal 'protein folding code error network' is found to have one major, highly dominant, 'spherical' component, a minor attachment handle in the Morse Theory sense, and as many as three additional subminor handles. The basic amyloid folding code error network appears to be more complicated, of genus two, giving the eightfold symmetry of the steric zipper. Like many before us, we conjecture that the elaborate cellular regulatory machinery associated with the endoplasmic reticulum and heat shock proteins is needed to prevent transition between these two thermodynamically 'natural' sets of protein conformations, and that its corrosion by aging accounts for the subsequent onset of many protein folding disorders. These results suggest markedly different evolutionary trajectories for the genetic and protein folding codes.