Solution structure studies of monomeric human TIP47/perilipin-3 reveal a highly extended conformation.

Tail-interacting protein of 47 kDa (TIP47) has two putative functions: lipid biogenesis and mannose 6-phosphate receptor recycling. Progress in understanding the molecular details of these two functions has been hampered by the lack of structural data on TIP47, with a crystal structure of the C-terminal domain of the mouse homolog constituting the only structural data in the literature so far. Our studies have first provided a strategy to obtain pure monodisperse preparations of the full-length TIP47/perilipin-3 protein, as well as a series of N-terminal truncation mutants with no exogenous sequences. These constructs have then enabled us to obtain the first structural characterization of the full-length protein in solution. Our work demonstrates that the N-terminal region of TIP47/perilipin-3, in contrast to the largely helical C-terminal region, is predominantly β-structure with turns and bends. Moreover, we show that full-length TIP47/perilipin-3 adopts an extended conformation in solution, with considerable spatial separation of the N- and C-termini that would likely translate into a separation of functional domains.