Figure 1.
Structure of Proline and Related Homologues.
This figure shows the structures of proline (a), L-azetidine-2-carboxylic acid (Aze) (b), ß-lactam (c), nicotianamine (d), and mugineic acid (e). Aze is the lower homologue of proline. Its ring has only four members instead of five. Plants synthesize Aze as essential constituents of the two metal chelating molecules, nicotianamine and mugineic acid. These compounds trap metal ions in the soil and transport them to various plant parts. Aze is in particularly high concentrations in the bulbous roots of many plants, making its way into the human and lifestock food supply. Aze exerts its toxic effects by eluding the proof-reading function of the prolyl tRNA synthetases, allowing it to be misincorporated into nascent peptides or proteins in which it replaces proline. When Aze replaces proline, it can change protein structure, function, and antigenicity. This molecular mimicry is analagous to the other 4-member nitrogen containing ring of ß-lactam, which exerts its bactericidal effects by mimicking a D-Ala-D-Ala sequence of a transpeptidase, irreversibly blocking its role in bacterial cell wall synthesis. The role of Aze in human health is yet to be established.
Figure 2.
Distribution of Proline Across Proteome.
(a) Counts of amino acids binned by their proportion of proline. (b) Counts of amino acids binned by their proportion of polyproline. (c) Counts of polyproline spans binned by their length.
Figure 3.
Distribution of Amino Acids by Protein Length Across Human Proteome.
The counts of each amino acid as a function of relative length are shown with each letter corresponding to the appropriate amino acid. Each protein was divided into 100 segments and the total count of each amino acid in each segment was summed across the proteome. For example, a 200 amino acid long protein with a serine in position 3 and a lysine in position 4 would add a count of one S and one L in the 2% bin along the horizontal axis. Proline, P, peaks in prevalence at the 2% of length position, with 8,215 prolyl residues of a total of 108,671 amino acids (7.6% proline). The vertical axis was normalized to reflect a percent frequency.
Table 1.
Association of functional classes with polyproline long repeats.
Figure 4.
Repeated TWEAZR Motif in ZNF729.
(a) The 28-amino-acid motif (TWEAZR) repeated 32 times in ZNF729. (b) Ribbon cartoon showing the likely structure of the conserved zinc finger motif based on homology with similar zinc finger structures. The cysteine residues are marked in green, the histidine in blue, and the proline in red. We propose that cis-trans isomerization of the proline can move the downstream portion of the zinc finger domain and alters the contact of some residues with specific nucleic acids. (c) The logo for the TWEAZR motif in ZNF729.
Table 2.
Abundance of Zinc Finger Proteins with Polyproline Spans.
Table 3.
Conservation and variation in the amino acids in the repeating motif in ZNF729.