E ankyrins have distinct and non-overlapping functions in precise 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 towards the underlying cytoskeleton, ankyrin dysfunction is closely associated to significant human illnesses. As an example, loss-of-function mutations can cause hemolytic anemia (Gallagher, 2005), various cardiac diseases 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;3:e04353. DOI: 10.7554/eLife.1 ofResearch articleBiochemistry | Biophysics and structural biologyeLife digest Proteins are 943-80-6 site produced up of smaller sized developing blocks named amino acids which can be linkedto form extended chains that then fold into distinct shapes. Every protein gets its exceptional identity in the number and order with the amino acids that it includes, but 1101854-58-3 Biological Activity diverse proteins can include comparable arrangements of amino acids. These similar sequences, called motifs, are usually short and generally mark the websites inside proteins that bind to other molecules or proteins. A single protein can contain numerous motifs, like a number of repeats on the identical motif. One particular prevalent motif is called the ankyrin (or ANK) repeat, that is found in 100s of proteins in different species, including bacteria and humans. Ankyrin proteins perform a selection of critical functions, such as connecting proteins in the cell surface membrane to a scaffold-like structure underneath the membrane. Proteins containing ankyrin repeats are known to interact having a diverse selection of other proteins (or targets) that happen to be various in size and shape. The 24 repeats identified in human ankyrin proteins seem to have essentially remained unchanged for the last 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 when it was bound either to a regulatory fragment from a different ankyrin protein or to a area of a target protein (which transports sodium ions in and out of cells). The ankyrin repeats have been shown to type an extended `left-handed helix’: a structure that has also been noticed in other proteins with various repeating motifs. Wang, Wei et al. discovered that the ankyrin protein fragment bound towards the inner surface with the a 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 consists of numerous binding sites which will be applied, in different combinations, to enable ankyrins to interact with diverse proteins. Other proteins with extended sequences of repeats are widespread in nature, but uncovering the structures of these proteins is technically challenging. Wang, Wei et al.’s findings may possibly reveal new insights in to the functions of a lot of of such proteins inside a wide array of living species. Moreover, the new structures could assist clarify why certain mutations inside the genes that encode ankyrins (or their binding targets) may cause a variety of diseases in humans–including heart illnesses and psychiatric issues.DOI: ten.7554/eLife.04353.The wide.