Eugenia Mileykovskaya, PhD

兴趣范围

beplay苹果手机能用吗研究兴趣

beplay苹果手机能用吗研究信息

Our research is directed at understanding the role phospholipids play in organization of membrane proteins into macro-molecular machines. This assumes membrane lateral heterogeneity and formation of a network of membrane lipid-protein domains. We are using two models, the highly specialized membrane of yeast mitochondria, containing enzymes of the oxidative phosphorylation system, and the multifunctional bacterial membrane of Escherichia coli. The bacterial model is employed to study interaction of phospholipids with the cytoskeletal proteins of the bacterial division machinery. We investigate the mutual influence of amphitropic cell division proteins, which undergo dynamic oligomerization on the membrane surface, and membrane phospholipids, in the formation of dynamic lipid-protein domains. Our hypothesis is that the domains enriched by the anionic phospholipid cardiolipin (CL) play an important role in the bacterial cell division process. We also participate in a collaborative study to explore the action of a number of antimicrobial agents, the primary target of which is anionic phospholipids. Using the yeast model we investigate the role of CL in organization of electron transfer enzymes of the respiratory chain into supra-molecular structures termed as supercomplexes. Although the existence of respiratory supercomplexes is now generally accepted, the factors that regulate their formation and function are not well understood. Earlier, using a yeast model system, we discovered a direct correlation between CL levels and levels of respiratory supercomplexes thus showing that CL played a central role in supercomplex formation. Subsequently, a significant amount of data have been accumulated by different groups demonstrating that in many diseases, including Barth syndrome, neurodegenerative diseases, heart failure, and cancer, the defects in respiratory supercomplex formation are associated with reduced levels of CL or alterations in the landscape of CL species. Currently we focus on understanding the precise molecular mechanism for the CL-dependent formation and stabilization of the supercomplexes. Our approach combines biochemical, structural and computational studies. We have performed the first in vitro reconstitution of the yeast supercomplex composed of Complex III and two Complexes IV from the purified individual complexes in CL containing liposomes. In our recent structural studies a 3D density map of the yeast respiratory supercomplex composed of Complex III and two Complexes IV was obtained by electron cryo-microscopy and image processing. The structure shows gaps between the transmembrane-localized interfaces of individual complexes consistent with the large excess of CL in the supercomplex over tightly bound CL in the structure of individual respiratory complexes. We hypothesize that non-integral CL molecules play an important role in supercomplex formation and may be involved in regulation of its stability under metabolic conditions where CL levels fluctuate.

选定的参考

• Mileykovskaya E.，Dowhan W.“通过使用Cardiolipin特异性荧光染料10-N-Nonyl accridine橙橙橙色的大肠杆菌中磷脂结构域的可视化”，J。Bacteriol。182：11​​72-1175，2000。
• Mileykovskaya E., Dowhan W., Birke R.L., Zheng D., Lutterodt L.,Haines T.H. “Cardiolipin binds nonyl acridine orange by aggregating the dye at exposed hydrophobic domains on bilayer surfaces”, FEBS Lett. 507: 187-190, 2001.
• 张M.，Mileykovskaya E., Dowhan, W. “Gluing the Respiratory Chain Together: Cardiolipin Facilitates Supercomplex Formation in the Inner Mitochondrial Membrane”, J. Biol. Chem. 277: 43553-43556, 2002.
• Mileykovskaya E.，Fishov I.，Fu X.，Corbin B.D.，Margolin W.，Dowhan W.“磷脂组成对体外和体内思维膜相互作用的影响”，J。Biol。化学278：22193-22198，2003。
• Norris V.，Woldringh C.，Mileykovskaya E.“A hypothesis to explain division site selection in Escherichia coli by combining nucleoid occlusion and Min”, FEBS Lett. 561: 3-10, 2004.
• Dowhan，W。，Mileykovskaya，E。, and Bogdanov, M. “Diversity and Versatility of Lipid-Protein Interactions Revealed by Molecular Genetic Approaches”, Biophys. Biochim. Acta 1666:19-39, 2004.
• 张M.，Mileykovskaya E.，Dowhan W.“ Cardiolipin对于复合物III和IV的组织至关重要。化学280：29403-29408，2005。
• Mileykovskaya，E。, Zhang, M., and Dowhan, W. “Cardiolipin in Energy Transducing Membranes”, Biochemistry (Moscow) 70:154-158, 2005.
• Mileykovskaya，E。and Dowhan, W. “Role of membrane lipids in bacterial division-site selection”, Curr. Opin. Microbiol. 8:135-142, 2005.
• Mileykovskaya E.“大肠杆菌渗透压转运蛋白的亚细胞定位：关注心磷脂膜结构域”，摩尔。微生物。64：1419-1422，2007。
• Bogdanov，M.，Mileykovskaya E.和Dowhan，W。“膜蛋白组装中的脂质和蛋白质超复合物的组织：对健康和疾病的脂质中对脂质连接疾病的影响”；系列：亚细胞生物化学49：197-239，2008。
• Mazor，S.，Regev，T.，Mileykovskaya E.，Margolin，W.，Dowhan，W.，Fishov，I。“思维 - 膜相互作用的相互影响：I。由心灵结合引起的膜特性的变化”，生物化学。生物。ACTA 1778：2496-2505，2008。
• Mileykovskaya E.和Dowhan W.，“原核生物和真核生物中的Cardiolipin膜结构域”，Biochim。生物。ACTA 1788：2084-2091，2009。
• Mileykovskaya E.和Margolin W.，第5-1章：“细胞分裂”。pp 149-177在“大肠杆菌和枯草芽孢杆菌；分子微生物学的前沿修订了”，编辑：Yoshito Sadaie和Kouji Matsumoto，研究路标，喀拉拉邦，印度，2012年。beplay苹果手机能用吗
• Mileykovskaya E., Penczek P.A., Fang J., Mallampalli V.K., Sparagna G.C., Dowhan W. “Arrangement of the respiratory chain complexes in Saccharomyces cerevisiae supercomplex III2IV2 revealed by single particle cryo-electron microscopy”, J. Biol. Chem. 287: 23095-23103, 2012.
• Tran T.T., Panesso D., Mishra N.N.,Mileykovskaya E., Guan Z., Munita J.M., Reyes J., Diaz L., Weinstock G.M., Murray B.E., Shamoo Y., Dowhan W., Bayer A.S., Arias C.A.“Daptomycin-resistant Enterococcus faecalis diverts the antibiotic molecule from the division septum and remodels cell membrane phospholipids” MBio., 4(4). pii: e00281-13, 2013.
• Bazan S.，Mileykovskaya E.，Mallampalli V.K.，Hecock P.，Sparagna G.C.，Dowhan W.“来自纯化的苏氏酵母复合物III和IV的呼吸超复杂的Cardiolipin依赖性重新复杂”，J。Biol”，J.Biol。化学288：401-411，2013
• Mileykovskaya E.，Dowhan，W。“线粒体呼吸超杂复合的心磷脂依赖性形成”化学。物理。脂质2013年出版社。