E ankyrins have distinct and non-overlapping functions in certain membrane domains coordinated by ankyrin-spectrin networks (Mohler et al., 2002; Abdi et al., 2006; He et al., 2013). As ankyrins are adaptor 563-41-7 web proteins linking membrane proteins towards the underlying cytoskeleton, ankyrin dysfunction is closely related to significant human illnesses. By way of example, loss-of-function mutations may cause hemolytic anemia (Gallagher, 2005), various cardiac diseases such as a number of 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;3:e04353. DOI: ten.7554/eLife.1 ofResearch articleBiochemistry | Biophysics and structural biologyeLife digest Proteins are created up of smaller creating blocks named amino acids that happen to be linkedto form long chains that then fold into particular shapes. Each protein gets its exclusive identity in the quantity and order on the amino acids that it contains, but various proteins can include similar arrangements of amino acids. These similar sequences, called motifs, are usually short and normally mark the web pages inside proteins that bind to other molecules or proteins. A single protein can contain a lot of motifs, like numerous H2G Technical Information repeats with the exact same motif. One particular common motif is known as the ankyrin (or ANK) repeat, which is discovered in 100s of proteins in various species, which includes bacteria and humans. Ankyrin proteins perform a array of crucial functions, for example connecting proteins inside the cell surface membrane to a scaffold-like structure underneath the membrane. Proteins containing ankyrin repeats are recognized to interact using a diverse range of other proteins (or targets) which can be diverse in size and shape. The 24 repeats identified in human ankyrin proteins seem to have essentially remained unchanged for the final 500 million years. As such, it remains unclear how the conserved ankyrin repeats can bind to such a wide range 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 area 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 that has also been noticed in other proteins with distinct repeating motifs. Wang, Wei et al. discovered that the ankyrin protein fragment bound towards the inner surface of the part of the helix formed by the very first 14 ankyrin repeats. The target protein area also bound to the helix’s inner surface. Wang, Wei et al. show that this surface contains a lot of binding web sites that will be utilized, in unique combinations, to permit ankyrins to interact with diverse proteins. Other proteins with extended sequences of repeats are widespread in nature, but uncovering the structures of those proteins is technically challenging. Wang, Wei et al.’s findings may reveal new insights in to the functions of several of such proteins in a wide selection of living species. Additionally, the new structures could aid explain why specific mutations in the genes that encode ankyrins (or their binding targets) may cause many diseases in humans–including heart illnesses and psychiatric disorders.DOI: ten.7554/eLife.04353.The wide.