The Coronin Family of Proteins

McArdle, Bernadette, Hofmann, Andreas, Bernadette McArdle, Andreas Hofmann

Until recently, structural information about coronins was scarce and the earlier identification of five WD40 repeats gave rise to a structural prediction of a five-bladed beta propeller for the N-terminal domain of these proteins. More detailed analyses revealed the presence of seven WD40 repeats and the hypothesis of a seven-bladed beta propeller structure. This model has recently been validated due to structural information from crystal structures of C-terminally truncated coronin 1 (1A), as well as its C-terminal coiled coil domain. Further structural information is available only indirectly from binding and functional studies.Phosphorylation at distinct serine and tyrosine residues seems to be a common theme for various coronins. There are indications that this modification regulates the quaternary structure of coronin 3 (1C) and thus has implications for the cellular localisation and the general link between signalling and cytoskeletal remodelling. Similarly, phosphorylation-dependent sorting sequences recently discovered on coronin 7 might prove important for the molecular mechanisms of the longer coronins.A matter that will require further clarification is the localisation of protein binding sites on coronins. While earlier reports presented a rather diverse map of actin binding sites, more recent studies, including the crystal structure of the coronin 1 N-terminal domain, deliver more detailed information in this respect. Interaction sites for other target proteins, such as Arp2/3, remain to be identified. Also, while membrane binding is a known feature of coronins, further details as to the binding sites and molecular level events remain to be elucidated. The N-terminal WD40 repeat domain seems to be the membrane-interacting domain, but other domains might provide regulatory effects, most likely by posttranslational modification, in a fashion that is specific for each coronin.In this chapter, we provide a structural overview of coronins 1 (1A), 2 (1B), 3 (1C) and 7 and also present results of our recent efforts to obtain structural models of coronins 3 and 7. Possible implications of these models on the function of these proteins are discussed.