Junedi Sendy, Yasuhara Kazuma, Nagao Satoshi, Kikuchi Jun-Ichi, Hirota Shun
Graduate School of Materials Science, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192 (Japan).
Chembiochem. 2014 Mar 3;15(4):517-21. doi: 10.1002/cbic.201300728. Epub 2014 Jan 21.
Monomeric cyt c has been reported to bind to the mitochondrial membrane by electrostatic and hydrophobic interactions with anionic phospholipids. We have previously shown that domain-swapped oligomeric cyt c retains the secondary structure of the monomer, and its surface possesses a larger area and more charges compared to the monomer. However, the effect of oligomerization of cyt c on cells has yet to be revealed. Herein, we investigated the interaction of oligomeric cyt c with anionic phospholipid-containing vesicles and the outer membrane of HeLa cells. Oligomeric cyt c interacted more strongly than monomeric cyt c with anionic phospholipid-containing vesicles and the outer membrane of HeLa cells. Oligomeric cyt c induced lateral phase separation of lipids in LUVs and GUVs, thereby leading to membrane disruption, whereas monomeric cyt c did not. Morphological changes in HeLa cells resulted from interaction with oligomeric cyt c, but little from interaction with the monomer. These results show that domain-swapped oligomeric proteins might exhibit properties different to those of monomer in cell systems.
据报道，单体细胞色素c通过与阴离子磷脂的静电和疏水相互作用与线粒体膜结合。我们之前已经表明，结构域交换的寡聚细胞色素c保留了单体的二级结构，并且与单体相比，其表面具有更大的面积和更多的电荷。然而，细胞色素c寡聚化对细胞的影响尚未揭示。在此，我们研究了寡聚细胞色素c与含阴离子磷脂的囊泡和HeLa细胞外膜的相互作用。寡聚细胞色素c与含阴离子磷脂的囊泡和HeLa细胞外膜的相互作用比单体细胞色素c更强。寡聚细胞色素c诱导了大单层囊泡（LUVs）和巨型单层囊泡（GUVs）中脂质的侧向相分离，从而导致膜破坏，而单体细胞色素c则不会。HeLa细胞的形态变化是由与寡聚细胞色素c的相互作用引起的，而与单体的相互作用则几乎没有影响。这些结果表明，结构域交换的寡聚蛋白在细胞系统中可能表现出与单体不同的性质。
