Peptide-plane flipping in proteins

Abstract

A peptide-plane flip is a large-scale rotation of the peptide plane that takes the phi,psi angles at residues i and i + 1 to different structural regions in the Ramachandran plot with a comparatively small effect on the relative orientation of their side chains. This phenomenon, which is expected to play an important role during the early stages of protein folding, has been investigated using 76 proteins for which two high-resolution X-ray conformations are available. Peptide-plane flips are identified by looking for those cases where changes in /psi(i)/ + /phi(i + 1)/ are large (>200 degrees), but changes in /psi(i) + phi(i + 1)/ are comparatively small (<50 degrees). Of a total of 23 cases, the most common peptide-plane flip was identified to be the type I to type II beta-turn interconversion. Although individually rarer, there are many other types of flips that are collectively more common. Given the four main accessible regions alpha(R), alpha(L), beta and epsilon, identified from the phi,psi distribution corresponding to non-hydrogen-bonded peptide planes, 32 main types of peptide-plane flip are identified. Only 8 of these are "passive," in that they require only relatively minor adjustments in the orientation of adjacent peptide planes. Of these, only the type I to type II beta-turn interconversion, denoted, beta(i) + alpha(L)(i + 1) <--> alpha(R)(i) + alpha(R)(i + 1), and the rarer alpha(R)(i) + alpha(L)(i + 1) <--> beta(i) + alpha(R)(i + 1), do not involve the epsilon region. "Active" peptide-plane flips affect the orientation of adjacent peptide planes. The flip, alpha(L)(i) + alpha(L)(i + 1) <--> beta(i) + beta(i + 1), of which one example was found, shows how concerted peptide-plane flips can convert the alpha(L) structure to the beta structure without affecting the relative orientations of the side chains.

Fig. 1.

A φ_{i + 1},ψ_i plot showing transitions that satisfy inequality 3, indicated by the broken lines and continuous lines, and those that satisfy inequalities 3 and 4, indicated by continuous lines only. Those indicated by triangles joined by continuous lines are group 1 transitions; those by squares and continuous lines, group 2; all others are indicated by small circles joined by broken lines. Group 1 transitions have ψ_i in the extended region when φ_{i + 1} is positive, whereas group 2 transitions have ψ_i in the α-helix regions when φ_{i + 1} is positive. The background gray dots are the φ_{i + 1},ψ_i values taken from the first of each of the 76 pairs of conformations. The path taken by the transitions is almost certainly not the one indicated by the lines that cross the high energy region around φ = 0°, but follows the direction indicated by the arrow through φ = −180°,180°, applying the usual periodicity of torsion space.

Fig. 2.

(a) Ramachandran plots for the group 1 flips and (b) group 2 flips. (a) Residue i is in the β or ɛ region, when residue i + 1 has positive φ values. (b) Residue i is in the α regions when residue i + 1 has positive φ values. Symbols joined by continuous lines show changes in φ_i,ψ_i for each peptide-plane flip. Equivalent symbols joined by broken lines show changes in φ_{i + 1},ψ_{i + 1} for the same flip. The lines joining the symbols do not necessarily indicate the paths taken. The vertical and horizontal arrows indicate the general direction of the low energy paths taken at residues i and i + 1, respectively. The background gray dots are the φ_i,ψ_i values taken from the first structure of the 76 pairs.

Fig. 3.

Ramachandran plot, where black circles give φ_i,ψ_i values and gray circles φ_{i + 1},ψ_{i + 1} values for nonbonding peptide planes taken from the first structure of the 76 pairs. The peptide plane formed from residues i and i + 1 is defined to be nonbonding when the carbonyl group of residue i and the amide group of residue i + 1 both have electrostatic interactions greater than −0.2 kcal/mole according to the DSSP definition of hydrogen-bonding energy (Kabsch and Sander 1983).