Abstract
Stable single-alpha helices (SAHs) are versatile structural elements in many prokaryotic and eukaryotic proteins acting as semi-flexible linkers and constant force springs. This way SAH-domains function as part of the lever of many different myosins. Canonical myosin levers consist of one or several IQ-motifs to which light chains such as calmodulin bind. SAH-domains provide flexibility in length and stiffness to the myosin levers, and may be particularly suited for myosins working in crowded cellular environments. Although the function of the SAH-domains in human class-6 and class-10 myosins has well been characterised, the distribution of the SAH-domain in all myosin subfamilies and across the eukaryotic tree of life remained elusive. Here, we analysed the largest available myosin sequence dataset consisting of 7919 manually annotated myosin sequences from 938 species representing all major eukaryotic branches using the SAH-prediction algorithm of Waggawagga, a recently developed tool for the identification of SAH-domains. With this approach we identified SAH-domains in more than one third of the supposed 79 myosin subfamilies. Depending on the myosin class, the presence of SAH-domains can range from a few to almost all class members indicating complex patterns of independent and taxon-specific SAH-domain gain and loss.
Highlights
Helices, which are not buried within globular structures or coiled-coil helical dimers, usually need networks of charge interactions for stabilization in water [1,2,3,4,5]
Mammalian myosins from the class-6 and class-10 subfamilies have experimentally been shown to contain single-alpha helices (SAHs)-domains subsequent to the IQ-motif regions functioning as extended levers and constant force springs [14,17,23,24]
All stabilization values within a given sequence window are summed up and the sum is subsequently normalized against an idealised SAH-domain containing only strong interactions to compute an SAH-score for the central amino acid of the sequence window [25]
Summary
Helices, which are not buried within globular structures or coiled-coil helical dimers, usually need networks of charge interactions for stabilization in water [1,2,3,4,5]. Additional stability is obtained through networks of oppositely charged residues in (i, i+3, i +6), (i, i+3, i+7), (i, i+4, i+7), or (i, i+4, i+8) distances [9,10] In addition to these poly-alanine based peptides, studies have been performed on peptides with complex amino acid distributions [11,12]. Studies on natural proteins known to contain stable single α-helices (SAHs) have shown that the respective sequence regions mainly consist of repeated patterns of negatively and positively charged residues [13,14,15,16,17,18]. Mammalian myosins from the class-6 and class-10 subfamilies have experimentally been shown to contain SAH-domains subsequent to the IQ-motif regions functioning as extended levers and constant force springs [14,17,23,24]. Depending on the myosin class, the presence of SAH-domains can range from a few to almost all class members indicating complex patterns of independent and taxon-specific SAH-domain gain and loss
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