The C terminus of apolipoprotein A-V modulates lipid-binding activity
The C terminus of apolipoprotein A-V modulates lipid-binding activity
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DOI：
10.1074/jbc.m611797200
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发表时间：
2007-05-25
影响因子：
4.8
通讯作者：
Ryan, Robert O.
中科院分区：
文献类型：
--
作者：
Beckstead, Jennifer A.;Wong, Kasuen;Ryan, Robert O.
Human apolipoprotein A-V (apoA-V) is a potent modulator of plasma triacylglycerol (TG) levels. To probe different regions of this 343-amino-acid protein, four single Trp apoA-V variants were prepared. The variant with a Trp at position 325, distal to the tetraproline sequence at residues 293-296, displayed an 11-nm blue shift in wavelength of maximum fluorescence emission upon lipid association. To evaluate the structural and functional role of this C-terminal segment, a truncated apoA-V comprising amino acids 1-292 was generated. Far UV circular dichroism spectra of full-length apoA-V and apoA-V-(1-292) were similar, with similar to 50% alpha-helix content. In guanidine HCl denaturation experiments, both full-length and truncated apoA-V yielded biphasic profiles consistent with the presence of two structural domains. The denaturation profile of the lower stability component ( but not the higher stability component) was affected by truncation. Truncated apoA-V displayed an attenuated ability to solubilize L-alpha-dimyristoylphosphatidylcholine phospholipid vesicles compared with full-length apoA-V, whereas a peptide corresponding to the deleted C-terminal segment displayed markedly enhanced kinetics. The data support the concept that the C-terminal region is not required for apoA-V to adopt a folded protein structure, yet functions to modulate apoA-V lipid-binding activity; therefore, this concept may be relevant to the mechanism whereby apoA-V influences plasma TG levels.
