Lawrence Berkeley National Laboratory
Structural basis of the lipid transfer mechanism of phospholipid transfer protein (PLTP).
- Author(s): Zhang, Meng
- Zhai, Xiaobo
- Li, Jinping
- Albers, John J
- Vuletic, Simona
- Ren, Gang
- et al.
Published Web Locationhttps://doi.org/10.1016/j.bbalip.2018.06.001
Human phospholipid transfer protein (PLTP) mediates the transfer of phospholipids among atheroprotective high-density lipoproteins (HDL) and atherogenic low-density lipoproteins (LDL) by an unknown mechanism. Delineating this mechanism would represent the first step towards understanding PLTP-mediated lipid transfers, which may be important for treating lipoprotein abnormalities and cardiovascular disease. Here, using various electron microscopy techniques, PLTP is revealed to have a banana-shaped structure similar to cholesteryl ester transfer protein (CETP). We provide evidence that PLTP penetrates into the HDL and LDL surfaces, respectively, and then forms a ternary complex with HDL and LDL. Insights into the interaction of PLTP with lipoproteins at the molecular level provide a basis to understand the PLTP-dependent lipid transfer mechanisms for dyslipidemia treatment.