Figure 5.

Model of spartin's role in the activation and recruitment of atrophin-1-interacting protein 4 (AIP4) to lipid droplets and subsequent adipophilin ubiquitination. AIP4 in the absence of binding to spartin is in an autoinhibited conformation (left panel). Our heuristic model predicts that spartin, via its PPAY motif, recruits AIP4 to lipid droplets and alters AIP4 conformation, which leads to its increased enzymatic activity. The ubiquitination of resident proteins present on lipid droplets, such as adipophilin, is facilitated by the spartin-mediated recruitment and activation of AIP4 (right panel). I, II, III, IV = WW-I, WW-II, WW-III, and WW-IV domains; ADRP = adipophilin (also known as adipose differentiation-related protein); C2 = calcium binding domain; HECT = homologues of the E6-associated protein C-terminal domain; LD = lipid droplet; PPAY = PPAY motif of spartin; PRR = proline-rich domain; Ub = ubiquitin.