E ankyrins have distinct and non-overlapping functions in distinct membrane domains coordinated by ankyrin-spectrin networks (Mohler et al., 2002; Abdi et al., 2006; He et al., 2013). As ankyrins are adaptor proteins linking membrane proteins to the underlying cytoskeleton, ankyrin dysfunction is closely related to severe human diseases. By way of example, loss-of-function mutations may cause hemolytic anemia (Gallagher, 2005), many cardiac ailments like numerous cardiac arrhythmia syndromes and sinus node dysfunction (Mohler et al., 2003, 2007; Le Scouarnec et al., 2008; Hashemi et al., 2009), bipolar disorder (Ferreira et al., 2008; Dedman et al., 2012; Rueckert et al., 2013), and autism spectrum disorder (Iqbal et al., 2013; Shi et al., 2013).Wang et al. eLife 2014;three:e04353. DOI: ten.7554/eLife.1 ofResearch articleBiochemistry | Biophysics and structural biologyeLife digest Proteins are made up of smaller sized creating blocks named amino acids that happen to be linkedto kind Polyinosinic-polycytidylic acid References extended chains that then fold into particular shapes. Each and every protein gets its special identity from the quantity and order with the amino acids that it contains, but unique proteins can include similar arrangements of amino acids. These similar sequences, called motifs, are often brief and normally mark the web pages within proteins that bind to other molecules or proteins. A single protein can contain lots of motifs, such as various repeats in the very same motif. One prevalent motif is named the ankyrin (or ANK) repeat, which can be found in 100s of proteins in distinctive species, such as bacteria and humans. Ankyrin proteins execute a range of essential functions, like connecting proteins within the cell surface membrane to a scaffold-like structure underneath the membrane. Proteins containing ankyrin repeats are identified to interact with a diverse range of other proteins (or targets) which are distinct in size and shape. The 24 repeats located in human ankyrin proteins seem to have basically remained unchanged for the final 500 million years. As such, it remains unclear how the conserved ankyrin repeats can bind to such a wide variety of protein targets. Now, Wang, Wei et al. have uncovered the three-dimensional structure of ankyrin repeats from a human ankyrin protein although it was bound either to a regulatory fragment from one more ankyrin protein or to a region of a target protein (which transports sodium ions in and out of cells). The ankyrin repeats were shown to kind an extended `left-handed helix’: a structure which has also been observed in other proteins with different repeating motifs. Wang, Wei et al. identified that the ankyrin protein fragment bound for the inner surface of the part of the helix formed by the initial 14 ankyrin repeats. The target protein area also bound to the helix’s inner surface. Wang, Wei et al. show that this surface includes lots of binding web pages that may be made use of, in distinct combinations, to permit ankyrins to interact with diverse proteins. Other proteins with long sequences of repeats are widespread in 7-Ethoxyresorufin MedChemExpress nature, but uncovering the structures of those proteins is technically challenging. Wang, Wei et al.’s findings might reveal new insights in to the functions of many of such proteins inside a wide range of living species. Furthermore, the new structures could enable clarify why particular mutations within the genes that encode ankyrins (or their binding targets) may cause numerous illnesses in humans–including heart diseases and psychiatric issues.DOI: 10.7554/eLife.04353.The wide.