Resonance assignments and secondary structure of apolipoprotein E C-terminal domain in DHPC micelles
Tóm tắt
Human apolipoprotein E (apoE) has been known to play a key role in the transport of plasma cholesterol and lipoprotein metabolism. It is an apolipoprotein of 299 amino acids with a molecular mass, ~34 kDa. ApoE has three major isoforms, apoE2, apoE3, and apoE4 which differ only at residue 112 or 158. ApoE consists of two independently folded domains (N-terminal and C-terminal domain) separated by a hinge region. The N-terminal domain and C-terminal domain of apoE are responsible for the binding to receptor and to lipid, respectively. Since the high resolution structures of apoE in lipids are still unavailable to date, we therefore aim to resolve the structures in lipids by NMR. Here, we reported the resonance assignments and secondary structure distribution of the C-terminal domain of wild-type human apoE (residue 195–299) in the micelles formed by dihexanoylphosphatidylcholine. Our results may provide a novel structural model of apoE in micelles and may shed new light on the molecular mechanisms underlying the apoE related biological processes.
Tài liệu tham khảo
Chen J, Li Q, Wang J (2011) Topology of human apolipoprotein E3 uniquely regulates its diverse biological functions. Proc Natl Acad Sci U S A 108(36):14813–14818
Dong LM, Weisgraber KH (1996) Human apolipoprotein E4 domain interaction. Arginine 61 and glutamic acid 255 interact to direct the preference for very low density lipoproteins. J Biol Chem 271(32):19053–19057
Dong LM, Wilson C, Wardell MR, Simmons T, Mahley RW, Weisgraber KH, Agard DA (1994) Human apolipoprotein E. Role of arginine 61 in mediating the lipoprotein preferences of the E3 and E4 isoforms. J Biol Chem 269(35):22358–22365
Dong LM, Parkin S, Trakhanov SD, Rupp B, Simmons T, Arnold KS, Newhouse YM, Innerarity TL, Weisgraber KH (1996) Novel mechanism for defective receptor binding of apolipoprotein E2 in type III hyperlipoproteinemia. Nat Struct Biol 3(8):718–722
Peters-Libeu CA, Newhouse Y, Hatters DM, Weisgraber KH (2006) Model of biologically active apolipoprotein E bound to dipalmitoylphosphatidylcholine. J Biol Chem 281(2):1073–1079
Peters-Libeu CA, Newhouse Y, Hall SC, Witkowska HE, Weisgraber KH (2007) Apolipoprotein E*dipalmitoylphosphatidylcholine particles are ellipsoidal in solution. J Lipid Res 48(5):1035–1044
Salzmann M, Wider G, Pervushin K, Wuthrich K (1999) Improved sensitivity and coherence selection for [15 N,1H]-TROSY elements in triple resonance experiments. J Biomol NMR 15(2):181–184
Sivashanmugam A, Wang J (2009) A unified scheme for initiation and conformational adaptation of human apolipoprotein E N-terminal domain upon lipoprotein binding and for receptor binding activity. J Biol Chem 284(21):14657–14666
Wetterau JR, Aggerbeck LP, Rall SC Jr, Weisgraber KH (1988) Human apolipoprotein E3 in aqueous solution. I. Evidence for two structural domains. J Biol Chem 263(13):6240–6248
Wilson C, Wardell MR, Weisgraber KH, Mahley RW, Agard DA (1991) Three-dimensional structure of the LDL receptor-binding domain of human apolipoprotein E. Science 252(5014):1817–1822
Wishart DS, Sykes BD (1994) The 13C chemical-shift index: a simple method for the identification of protein secondary structure using 13C chemical-shift data. J Biomol NMR 4(2):171–180
Wishart DS, Bigam CG, Yao J, Abildgaard F, Dyson HJ, Oldfield E, Markley JL, Sykes BD (1995) 1H, 13C and 15 N chemical shift referencing in biomolecular NMR. J Biomol NMR 6(2):135–140