Interfacial and Lipid Transfer Properties of Human Phospholipid Transfer Protein: Implications for the Transfer Mechanism of Phospholipids

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• 作者：Niko L. Setä ; lä ; Juha M. Holopainen ; Jari Metso ; Susanne K. Wiedmer ; Gebrenegus Yohannes ; Paavo K. J. Kinnunen ; Christian Ehnholm ; Matti Jauhiainen
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：February 6, 2007
• 年：2007
• 卷：46
• 期：5
• 页码：1312 - 1319
• 全文大小：297K
• 年卷期：v.46,no.5(February 6, 2007)
• ISSN：1520-4995

文摘

In circulation the phospholipid transfer protein (PLTP) facilitates the transfer of phospholipid-rich surface components from postlipolytic chylomicrons and very low density lipoproteins (VLDL) toHDL and thereby regulates plasma HDL levels. To study the molecular mechanisms involved in PLTP-mediated lipid transfer, we studied the interfacial properties of PLTP using Langmuir phospholipidmonolayers and asymmetrical flow field-flow fractionation (AsFlFFF) to follow the transfer of ¹⁴C-labeled phospholipids and [³⁵S]PLTP between lipid vesicles and HDL particles. The AsFlFFF methodwas also used to determine the sizes of spherical and discoidal HDL particles and small unilamellar lipidvesicles. In Langmuir monolayer studies high-activity (HA) and low-activity (LA) forms of PLTP associatedwith fluid phosphatidylcholine monolayers spread at the air/buffer interphase. Both forms also mediateddesorption of [¹⁴C]dipalmitoylphosphatidylcholine (DPPC) from the phospholipid monolayer into the bufferphase, even when it contained no physiological acceptor such as HDL. After the addition of HDL₃ to thebuffer, HA-PLTP caused enhanced lipid transfer to them. The particle diameter of HA-PLTP was ~6 nmand that of HDL₃ ~8 nm as determined by AsFlFFF analysis. Using this method, it could be demonstratedthat in the presence of HA-PLTP, but not LA-PLTP, [¹⁴C]DPPC was transferred from small unilamellarvesicles (SUV) to acceptor HDL₃ molecules. Concomitantly, [³⁵S]-HA-PLTP was transferred from thedonor to acceptor, and this transfer was not observed for its low-activity counterpart. These observationssuggest that HA-PLTP is capable of transferring lipids by a shuttle mechanism and that formation of aternary complex between PLTP, acceptor, and donor particles is not necessary for phospholipid transfer.