Abstract
Stable single-alpha helices (SAH-domains) function as rigid connectors and constant force springs between structural domains, and can provide contact surfaces for protein-protein and protein-RNA interactions. SAH-domains mainly consist of charged amino acids and are monomeric and stable in polar solutions, characteristics which distinguish them from coiled-coil domains and intrinsically disordered regions. Although the number of reported SAH-domains is steadily increasing, genome-wide analyses of SAH-domains in eukaryotic genomes are still missing. Here, we present Waggawagga-CLI, a command-line tool for predicting and analysing SAH-domains in protein sequence datasets. Using Waggawagga-CLI we predicted SAH-domains in 24 datasets from eukaryotes across the tree of life. SAH-domains were predicted in 0.5 to 3.5% of the protein-coding content per species. SAH-domains are particularly present in longer proteins supporting their function as structural building block in multi-domain proteins. In human, SAH-domains are mainly used as alternative building blocks not being present in all transcripts of a gene. Gene ontology analysis showed that yeast proteins with SAH-domains are particular enriched in macromolecular complex subunit organization, cellular component biogenesis and RNA metabolic processes, and that they have a strong nuclear and ribonucleoprotein complex localization and function in ribosome and nucleic acid binding. Human proteins with SAH-domains have roles in all types of RNA processing and cytoskeleton organization, and are predicted to function in RNA binding, protein binding involved in cell and cell-cell adhesion, and cytoskeletal protein binding. Waggawagga-CLI allows the user to adjust the stabilizing and destabilizing contribution of amino acid interactions in i,i+3 and i,i+4 spacings, and provides extensive flexibility for user-designed analyses.
Highlights
Stable single α-helices (SAHs) are extended helices that are not buried within globular structures or coiled-coil helical dimers [1,2,3,4,5,6,7,8]
Their most common function is to serve as rigid connectors or constant force springs between structural domains [1,2,3,4,5,7,9,10], but they provide contact surfaces for protein-protein and protein-RNA interactions [7,8]. The latter function has been found for the inner centromere protein Inner Centromere Protein (INCENP) and for many regions of spliceosomal proteins in various complexes formed during the pre-mRNA splicing cycle
Independent of any tertiary interactions, SAH-domains are stable and monomeric in polar solvents. These features distinguish SAH-domains from other proteins that fold into α-helices only in the presence of binding partners such as stathmin which is an intrinsically disordered protein lacking any stable fold in the absence of binding partners, but forms an extended αhelix when binding to tubulin dimers [11,12]
Summary
Stable single α-helices (SAHs) are extended helices that are not buried within globular structures or coiled-coil helical dimers [1,2,3,4,5,6,7,8]. Their most common function is to serve as rigid connectors or constant force springs between structural domains [1,2,3,4,5,7,9,10], but they provide contact surfaces for protein-protein and protein-RNA interactions [7,8]. To exclude misunderstandings because of term usage and to include all special cases, we will refer to these protein regions as SAH-domains on
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