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 towards the underlying cytoskeleton, ankyrin dysfunction is closely associated to 914471-09-3 supplier serious human ailments. As an example, loss-of-function mutations may cause hemolytic anemia (Gallagher, 2005), various cardiac illnesses which includes various 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: 10.7554/eLife.1 ofResearch articleBiochemistry | Biophysics and structural biologyeLife digest Proteins are produced up of smaller developing blocks known as amino acids that happen to be linkedto form long chains that then fold into distinct shapes. Each protein gets its one of a kind identity from the number and order in the amino acids that it contains, but unique proteins can contain related arrangements of amino acids. These equivalent sequences, known as motifs, are usually quick and usually mark the websites inside proteins that bind to other molecules or proteins. A single protein can include numerous motifs, such as various repeats of your identical motif. A single popular motif is known as the ankyrin (or ANK) repeat, which can be discovered in 100s of proteins in distinctive species, including bacteria and humans. Ankyrin proteins execute a range of crucial functions, like connecting proteins within the cell surface membrane to a scaffold-like structure underneath the membrane. Proteins containing ankyrin repeats are known to interact using a diverse selection of other proteins (or targets) which might be unique in size and shape. The 24 repeats identified 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 range of protein targets. Now, Wang, Wei et al. have uncovered the three-dimensional structure of ankyrin repeats from a human ankyrin protein though it was bound either to a regulatory fragment from yet another ankyrin protein or to a region of a target protein (which transports sodium ions in and out of cells). The ankyrin repeats have been shown to kind an extended `left-handed helix’: a structure that has also been noticed in other proteins with distinctive repeating motifs. Wang, Wei et al. found that the ankyrin protein fragment bound for the inner surface on the part of the helix formed by the very first 14 ankyrin repeats. The target protein region also bound towards the helix’s inner surface. Wang, Wei et al. show that this surface contains several binding web sites which will be utilized, in various combinations, to enable 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 challenging. Wang, Wei et al.’s findings could reveal new insights into the functions of lots of of such proteins within a wide selection of living species. Moreover, the new structures could enable clarify why particular mutations within the genes that encode ankyrins (or their binding targets) may cause a variety of illnesses in humans–including heart diseases and psychiatric disorders.DOI: ten.7554/eLife.04353.The wide.