Fundamentals of Molecular Biology. Part 1: Molecular Biology of the Cell - A. N. Ogurtsov 2011

Molecular Basis of Protein Function
Secondary Structure Repeats

Let us examine the Organization OF THE Spatial Structure of Proteins in greater detail.

Specific and frequently occurring combinations of secondary structures are called motifs or repeats. They serve as building blocks for the functional Tertiary Structure of proteins.

For example, the helix-loop-helix is a Ca²⁺-binding repeat characterized by the presence of specific hydrophilic residues at defined positions within the loop (Figure 115(a)), which is common to many calcium-binding and DNA-binding proteins.

In calcium-binding proteins such as calmodulin, the oxygen atoms of five amino acid residues and one Water molecule form an ionic bond with the Ca²⁺ ion. This motif has been identified in more than one hundred calcium-binding proteins and is also widely known in the literature as the EF hand.

Another widely distributed repeat is the zinc finger (Figure 115(6)). It is formed by three secondary protein structures—an α-Helix and two antiparallel β-sheets—which together form a finger-like structure stabilized by a zinc ion.

The Zn²⁺ ion coordinates with two Cysteine residues and two Histidine residues. Typically, the cysteine residues occupy positions 3 and 6, while the histidine residues occupy positions 20 and 24 of this 25-amino-acid motif. This repeat is most commonly found in RNA- or DNA-binding proteins.

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Figure 115 - Secondary structure repeats in proteins: a - helix-turn-helix, b - zinc finger, c - coiled coil

Many proteins, particularly fibrous ones, self-associate into oligomers using a third type of repeat known as a coiled coil. In such proteins, each polypeptide chain contains segments of a-helices where hydrophobic residues form periodic sequences along one face of the helix.

Such an a-helix is amphipathic, exhibiting increased Hydrophobicity on one side and enhanced hydrophilicity on the other. In aqueous solution, it is energetically favorable for two (or more) such helices to associate via hydrophobic interactions between their hydrophobic faces, resulting in The formation of a coiled coil (Figure 115(b)).

The presence of identical motifs in different proteins with similar Functions clearly points to an evolutionary Selection process that has preserved these advantageous structures. Currently, hundreds of repeats have been cataloged, and proteins are frequently classified According to the motifs present in their structures.