Figure 2

Key structural elements of arrestin proteins. This model of a generic arrestin molecule was generated in ViewerPro using the crystal structures of bovine rod arrestin [8] and arrestin2 [7]. The proximal carboxy-terminal tail (dark gray) missing in the structures has been modeled arbitrarily. (a) Intra-molecular interactions holding arrestin in the basal conformation. The structure is shown in ribbon representation, except for the residues in the polar core (blue, positive charges; red, negative charges) and the hydrophobic residues in the three-element interaction (yellow), which are shown in space-filling representation. Dark gray indicates the carboxy-terminal tail; magenta, the lariat loop in the carboxy-terminal domain containing two polar core negative charges; light brown, the inter-domain hinge (at the back of the molecule). The polar core is a cluster of five virtually solvent-excluded charged residues, which is unusual for a soluble protein; it includes one negative and one positive charge in the amino-terminal domain, two negative charges in the lariat loop of the carboxy-terminal domain and one positive charge in the carboxy-terminal tail. The three-element interaction is mediated by clusters of bulky hydrophobic residues in β-strand I, α-helix I and the carboxy-terminal tail. (b) Known interaction sites on the arrestin molecule. Receptor-binding elements: blue, positive charges that bind receptor-attached phosphates [70]; yellow, hydrophobic residues in β-strand X [71]; green, elements that determine receptor specificity [30]. Other elements: magenta, the clathrin-binding element in the proximal carboxy-terminal tail [27]; red, AP2-binding residues in the distal carboxy-terminal tail [28].