Journal Article

Proline: The Distribution, Frequency, Positioning, and Common Functional Roles of Proline and Polyproline Sequences in the Human Proteome

Rubenstein, Edward, Morgan, Alexander A.

2013

Overview

Proline is an anomalous amino acid. Its nitrogen atom is covalently locked within a ring, thus it is the only proteinogenic amino acid with a constrained phi angle. Sequences of three consecutive prolines can fold into polyproline helices, structures that join alpha helices and beta pleats as architectural motifs in protein configuration. Triproline helices are participants in protein-protein signaling interactions. Longer spans of repeat prolines also occur, containing as many as 27 consecutive proline residues. Little is known about the frequency, positioning, and functional significance of these proline sequences. Therefore we have undertaken a systematic bioinformatics study of proline residues in proteins. We analyzed the distribution and frequency of 687,434 proline residues among 18,666 human proteins, identifying single residues, dimers, trimers, and longer repeats. Proline accounts for 6.3% of the 10,882,808 protein amino acids. Of all proline residues, 4.4% are in trimers or longer spans. We detected patterns that influence function based on proline location, spacing, and concentration. We propose a classification based on proline-rich, polyproline-rich, and proline-poor status. Whereas singlet proline residues are often found in proteins that display recurring architectural patterns, trimers or longer proline sequences tend be associated with the absence of repetitive structural motifs. Spans of 6 or more are associated with DNA/RNA processing, actin, and developmental processes. We also suggest a role for proline in Kruppel-type zinc finger protein control of DNA expression, and in the nucleation and translocation of actin by the formin complex.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Actin / Actins - chemistry / Actins - genetics / Amino Acid Sequence / Amino acids / Biochemistry / Bioinformatics / Biology / Cell adhesion & migration / Chemistry / Computational Biology / Deoxyribonucleic acid / Dimers / DNA / DNA binding proteins / Evolution & development / Gene expression / Genes / Genomes / Helices / Humans / Influence functions / Kruppel protein / Kruppel-Like Transcription Factors - chemistry / Kruppel-Like Transcription Factors - genetics / Medicine / Microfilament Proteins - chemistry / Microfilament Proteins - genetics / Models, Molecular / Molecular biology / Molecular Sequence Data / Muscle proteins / Nitrogen / Peptides / Peptides - chemistry / Peptides - genetics / Polyproline / Proline / Proline - chemistry / Proline - genetics / Protein structure / Protein Structure, Secondary / Protein Structure, Tertiary / Proteins / Proteome - chemistry / Proteome - genetics / Proteomes / Residues / Ribonucleic acid / RNA / RNA processing / Signal transduction / Signaling / Transcription factors / Translocation / Trimers / Zinc / Zinc finger proteins