Molecular Biology: Protein Structure and Function - Stepanov V.M. 2005

Tertiary Protein Structure
Formation of the tertiary protein structure from secondary structure elements

The packing of Secondary Structure elements—a-helices, ß-sheet regions, and ß-turns—into the tertiary structure apparently follows certain specific rules.

Packing of a-helices. The surface of a-helices is typically characterized by The formation of ridges separated by depressions, or "grooves".

Most commonly, such a ridge is formed by amino acid side chains separated by three amino acid residues: the side chain of the i-th residue contacts the side chain of the (i+4)-th residue, the latter contacts the side chain of the (i+8)-th residue, and so on. Ridges formed by the i-, (i+3)-, and (i+6)-th residues are less frequent. The insertion of a ridge into the groove of a neighboring a-helix requires the angle between the helix axes to be approximately -50° for the i+4 type ridge, or 20° for the i+3 type. This ensures a sufficiently tight contact between side chains, as observed in real Proteins. The distance between the axes of contacting a-helices ranges from 6.8 to 12 Å depending on the length of the side chains (averaging 9 Å); the average interlocking ("nesting") depth of side chains at the contact interface is 2.3 Å. Thus, during the packing of a-helices in the Spatial Structure, only the terminal regions of The amino acid side chains directly interact.

Packing of a-helices and ß-structures. ß-Sheets in proteins are frequently twisted. The side groups of Amino Acids Forming such a structure create ridges, where the i-th residue interacts with the (i+2)-th, which in turn interacts with the (i+4)-th, and so forth. Any of the a-helix ridges described above can fit into the groove between two such ß-sheet ridges. This exact arrangement accounts for about 90% of experimentally observed a-helix–ß-Structure contacts, with their axes running parallel to each other.

Packing of ß-sheets. Two Types of ß-sheet interactions are known. One involves stacking one sheet on top of another with a rotation of -30°, while the other (referred to as orthogonal packing) involves a continuous ß-sheet bending and folding back on itself, with the angle between its segments approaching 90°. Sometimes this folding mode is described as a barrel or cylinder. The surfaces of ß-pleated sheets that mediate contact with other secondary structure elements are formed 60–70% by hydrophobic side chains of valine, leucine, isoleucine, phenylalanine, and Alanine. Evidently, branched chains are particularly well-suited for organizing hydrophobic contacts.