A pi helix (or ÃÂ-helix) is a type of secondary structure found in proteins. Discovered by crystallographer Barbara Low in 1952 and once thought to be rare, short ÃÂ-helices are found in 15% of known protein structures and are believed to be an evolutionary adaptation derived by the insertion of a single amino acid into an ñ-helix. Because such insertions are highly destabilizing, the formation of ÃÂ-helices would tend to be selected against unless it provided some functional advantage to the protein. ÃÂ-helices therefore are typically found near functional sites of proteins.
The amino acids in a standard ÃÂ-helix are arranged in a right-handed helical structure. Each amino acid corresponds to an 87ð turn in the helix (i.e., the helix has 4.1 residues per turn), and a translation of along the helical axis. Most importantly, the N-H group of an amino acid forms a hydrogen bond with the C=O group of the amino acid five residues earlier; this repeated i + 5 â i hydrogen bonding defines a ÃÂ-helix. Similar structures include the 3<sub>10</sub> helix (i + 3 â i hydrogen bonding) and the ñ-helix (i + 4 â i hydrogen bonding).
The majority of ÃÂ-helices are only 7 residues in length and do adopt regularly repeating (ÃÂ, ÃÂ) dihedral angles throughout the entire structure like that of ñ-helices or ò-sheets. Because of this, textbooks that provide single dihedral values for all residues in the ÃÂ-helix are misleading. Some generalizations can be made, however. When the first and last residue pairs are excluded, dihedral angles exist such that the àdihedral angle of one residue and the àdihedral angle of the next residue sum to roughly âÂÂ125ð. The first and last residue pairs sum to âÂÂ95ð and âÂÂ105ð, respectively. For comparison, the sum of the dihedral angles for a 3<sub>10</sub> helix is roughly âÂÂ75ð, whereas that for the ñ-helix is roughly âÂÂ105ð. Proline is often seen immediately following the end of ÃÂ-helices. The general formula for the rotation angle é per residue of any polypeptide helix with trans isomers is given by the equation
In principle, a left-handed version of the ÃÂ-helix is possible by reversing the sign of the (ÃÂ, ÃÂ) dihedral angles to (55ð, 70ð). This pseudo-"mirror-image" helix has roughly the same number of residues per turn (4.1) and helical pitch (). It is not a true mirror image, because the amino-acid residues still have a left-handed chirality. A long left-handed ÃÂ-helix is unlikely to be observed in proteins because, among the naturally occurring amino acids, only glycine is likely to adopt positive àdihedral angles such as 55ð.
Commonly used automated secondary structure assignment programs, such as DSSP, suggest <1% of proteins contain a ÃÂ-helix. This mis-characterization results from the fact that naturally occurring ÃÂ-helices are typically short in length (7 to 10 residues) and are almost always associated with (i.e. flanked by) ñ-helices on either end. Nearly all ÃÂ-helices are therefore cryptic in that the ÃÂ-helical residues are incorrectly assigned as either ñ-helical or as "turns". Recently developed programs have been written to properly annotate ÃÂ-helices in protein structures and they have found that 1 in 6 proteins (around 15%) do in fact contain at least one ÃÂ-helical segment.
Natural ÃÂ-helices can easily be identified in a structure as a "bulge" within a longer ñ-helix. Such helical bulges have previously been referred to as ñ-aneurisms, ñ-bulges, ÃÂ-bulges, wide-turns, looping outs and ÃÂ-turns, but in fact are ÃÂ-helices as determined by their repeating i + 5 â i hydrogen bonds. Evidence suggests that these bulges, or ÃÂ-helices, are created by the insertion of a single additional amino acid into a pre-existing ñ-helix. Thus, ñ-helices and ÃÂ-helices can be inter-converted by the insertion and deletion of a single amino acid. Given both the relatively high rate of occurrence of ÃÂ-helices and their noted association with functional sites (i.e. active sites) of proteins, this ability to interconvert between ñ-helices and ÃÂ-helices has been an important mechanism of altering and diversifying protein functionality over the course of evolution.
One of the most notable group of proteins whose functional diversification appears to have been heavily influenced by such an evolutionary mechanism is the ferritin-like superfamily, which includes ferritins, bacterioferritins, rubrerythrins, class I ribonucleotide reductases and soluble methane monooxygenases. Soluble methane monooxygenase is the current record holder for the most number of ÃÂ-helices in a single enzyme with 13 (PDB code 1MTY). However, the bacterial homologue of a Na<sup>+</sup>/Cl<sup>âÂÂ</sup> dependent neurotransmitter transporter (PDB code 2A65) holds the record for the most ÃÂ-helices in a single peptide chain with 8.