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Journal Articles Bioinformatics Year : 2022

The sequence context in poly-alanine regions: structure, function and conservation


Motivation: Poly-alanine (polyA) regions are protein stretches mostly composed of alanines. Despite their abundance in eukaryotic proteomes and their association to nine inherited human diseases, the structural and functional roles exerted by polyA stretches remain poorly understood. In this work we study how the amino acid context in which polyA regions are settled in proteins influences their structure and function. Results We identified glycine and proline as the most abundant amino acids within polyA and in the flanking regions of polyA tracts, in human proteins as well as in 17 additional eukaryotic species. Our analyses indicate that the non-structuring nature of these two amino acids influences the α-helical conformations predicted for polyA, suggesting a relevant role in reducing the inherent aggregation propensity of long polyA. Then, we show how polyA position in protein N-termini relates with their function as transit peptides. PolyA placed just after the initial methionine is often predicted as part of mitochondrial transit peptides, whereas when placed in downstream positions, polyA are part of signal peptides. A few examples from known structures suggest that short polyA can emerge by alanine substitutions in α-helices; but evolution by insertion is observed for longer polyA. Our results showcase the importance of studying the sequence context of homorepeats as a mechanism to shape their structure–function relationships.
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Dates and versions

hal-03778766 , version 1 (16-09-2022)



Pablo Mier, Carlos Elena-Real, Juan Cortés, Pau Bernadó, Miguel Andrade-Navarro. The sequence context in poly-alanine regions: structure, function and conservation. Bioinformatics, 2022, 38 (21), pp.4851-4858. ⟨10.1093/bioinformatics/btac610⟩. ⟨hal-03778766⟩
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