title: Solution structure studies of monomeric human TIP47/perilipin-3 reveal a highly extended conformation.
abstract: 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.
authors.affiliation: School of Molecular Bioscience, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Robert M G
authors.initials: RM
authors.lastname: Hynson
authors.forename: Cy M
authors.initials: CM
authors.lastname: Jeffries
authors.forename: Jill
authors.initials: J
authors.lastname: Trewhella
authors.forename: Simon
authors.initials: S
authors.lastname: Cocklin
mesh_terms: D002942:Circular Dichroism; D006801:Humans; D050505:Mutant Proteins / Q000737:chemistry*; D000070796:Perilipin-3; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012996:Solutions / Q000737:chemistry; D033921:Vesicular Transport Proteins / Q000737:chemistry*
chemical_list: D050505:Mutant Proteins; C038196:PLIN3 protein, human; D000070796:Perilipin-3; D012996:Solutions; D033921:Vesicular Transport Proteins