Principles of Protein Structure - G. Schulz 1982

Modes of polypeptide chain folding and association
Supersecondary structures
βξβ-Structural motif

The ßξß-unit is typically right-handed. Another common element usually classified as a supersecondary Structure is the ßξß-unit (also designated as ßxß). It consists of two parallel ß-sheets connected by a linker ξ. If the connection takes the form of a disordered chain (coil), the unit is denoted as ßcß; in the case of an α-Helix or a sheet of another ß-Structure, it is designated as ßaß or ßßß. As can be seen from Fig. 5.12a, such units are chiral. Globular Proteins contain almost exclusively right-handed ßξß-units [226–228]. This strongly indicates a preferred pathway of chain folding and a preferred mode of Secondary structure aggregation, i.e., supersecondary structure.

The preferred chirality can be explained by asymmetric steric constraints within the disordered polypeptide chain. Right-handed chirality is so advantageous that an explanation for it can be attempted. As noted above, the statistical weights of the conformational states of the polypeptide chain favor the (∅, ψ) angles of a ß-pleated sheet (Fig. 5.10a). Therefore, an extended chain in solution will typically have the same (∅, ψ) values and acquire the right-handed twist shown in Fig. 5.10b. If such a chain forms a loop, then with a general right-handed direction of chain twist, its twisting will increase with a left-handed loop and decrease with a right-handed one. This relationship is illustrated in Fig. 5.13. Additional twisting implies an increase in the ∅, ψ angles, as evident from a comparison of flat and pleated sheets. Starting from the (∅, ψ) angles in a pleated sheet, an increase in ∅ and ψ (moving toward the upper right part of the map) is significantly more hindered (Fig. 2.5) than a decrease in these angles (moving toward the lower left part). Thus, in the general case, a decrease in twist is favored, and the loop becomes right-handed. Obviously, once The formation of a right-handed loop has begun during the folding process, it is difficult to reverse the direction of twist. This is how the right-handed ßξß-unit is formed.

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Fig. 5.12. Supersecondary structures including ß-pleated sheets. Arrows indicate pleated sheets.

a — ßξß-unit. Left-handed (top) and right-handed (bottom) ξ connections of two parallel pleated sheets forming a left-handed twisted ß-structure (Fig. 5.10d). Typically, a right-handed connection is observed, b — Rossmann fold, representing two consecutively connected right-handed ßaß units. c — ß-zigzag, which is an antiparallel three-stranded ß-structure.

Fig. 5.13. Polypeptide chain folding scheme. Right-handed twisting of the polypeptide chain is incompatible with the formation of a right-handed loop. This can be verified by twisting a belt or a paper strip: a — a right-twisted paper strip, b — a strain-free left-handed loop is formed when bringing together the ends of the paper strip shown in Fig. a.

Combination of two consecutive ßaß-units. The Rossmann fold [229] (Fig. 5.12b) can also be classified as a supersecondary structure. It represents a special case of the ßξß-unit and consists of two consecutive ßaß-units. Such a ßaßaß-unit, which may contain a Hydrophobic core between the layers and helices, has been found in A number of proteins [186, 230–240].