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 associated to significant human illnesses. By way of example, loss-of-function mutations can cause hemolytic anemia (Gallagher, 2005), various cardiac illnesses which includes 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 1614-12-6 Epigenetic Reader Domain structural biologyeLife digest Proteins are created up of smaller sized developing blocks known as amino acids which are linkedto form lengthy chains that then fold into specific shapes. Each protein gets its distinctive identity in the number and order of the amino acids that it consists of, but various proteins can contain similar arrangements of amino acids. These equivalent sequences, known as motifs, are often quick and normally mark the websites inside proteins that bind to other molecules or proteins. A single protein can contain numerous motifs, such as many 918348-67-1 In stock repeats in the exact same motif. One common motif is known as the ankyrin (or ANK) repeat, which can be found in 100s of proteins in diverse species, like bacteria and humans. Ankyrin proteins carry out a range of crucial functions, for example connecting proteins within the cell surface membrane to a scaffold-like structure underneath the membrane. Proteins containing ankyrin repeats are known to interact with a diverse selection of other proteins (or targets) which can be distinctive in size and shape. The 24 repeats identified in human ankyrin proteins seem to possess primarily remained unchanged for the last 500 million years. As such, it remains unclear how the conserved ankyrin repeats can bind to such a wide assortment 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 a further 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 type an extended `left-handed helix’: a structure that 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 first 14 ankyrin repeats. The target protein area also bound towards the helix’s inner surface. Wang, Wei et al. show that this surface consists of a lot of binding internet sites that will be utilized, in distinct combinations, to let ankyrins to interact with diverse proteins. Other proteins with lengthy sequences of repeats are widespread in nature, but uncovering the structures of these proteins is technically difficult. Wang, Wei et al.’s findings may possibly reveal new insights in to the functions of several of such proteins within a wide selection of living species. Furthermore, the new structures could enable clarify why certain mutations inside the genes that encode ankyrins (or their binding targets) may cause a variety of ailments in humans–including heart ailments and psychiatric problems.DOI: ten.7554/eLife.04353.The wide.