Atomic view of calcium-induced clustering of phosphatidylserine in mixed lipid bilayers.
Atomic view of calcium-induced clustering of phosphatidylserine in mixed lipid bilayers.
复制标题
DOI：
10.1021/bi1013694
复制
发表时间：
2011-03-29
期刊：
影响因子：
2.9
通讯作者：
Rienstra, Chad M.
中科院分区：
文献类型：
--
作者：
Boettcher, John M.;Davis-Harrison, Rebecca L.;Clay, Mary C.;Nieuwkoop, Andrew J.;Ohkubo, Y. Zenmei;Tajkhorshid, Emad;Morrissey, James H.;Rienstra, Chad M.
膜在生物过程中起着关键的调节作用，双层组成对许多膜相关蛋白的结合亲和力和催化活性产生显着影响。特别是，蛋白质参与不同的过程，如囊泡融合，细胞内信号级联，和血液凝固特异性相互作用的阴离子脂质，如磷脂酰丝氨酸（PS）的存在下的钙离子。虽然Ca 2+被怀疑诱导PS集群在混合磷脂双层，详细的结构影响，这种离子上的阴离子脂质没有建立。在这项研究中，结合魔角旋转（MAS）固体核磁共振（SSNMR）测量的同位素标记的丝氨酸头基在混合脂质双层的分子动力学（MD）模拟PS脂质双层在不同的抗衡离子的存在下，我们提供了现场解决的见解钙离子对脂质双层的结构和动力学的影响。Ca 2+诱导的混合双层中PS的构象变化在脂质体和Nanodisks，双层补丁的纳米级膜模拟观察。位点分辨多维相关SSNMR谱的双分子层含有13 C，15 N-标记的PS证明，Ca 2+离子促进两个主要的PS头基构象，这是很好地解决在二维13 C-13 C，15 N-13 C和31 P-13 C光谱。在存在或不存在Ca 2+的情况下，PS脂质双层进行MD模拟的结果提供了所观察到的光谱的基础上的构象效应的原子视图。
Membranes play key regulatory roles in biological processes, with bilayer composition exerting marked effects on binding affinities and catalytic activities of a number of membrane-associated proteins. In particular, proteins involved in diverse processes such as vesicle fusion, intracellular signaling cascades, and blood coagulation interact specifically with anionic lipids such as phosphatidylserine (PS) in the presence of Ca2+ ions. While Ca2+ is suspected to induce PS clustering in mixed phospholipid bilayers, the detailed structural effects of this ion on anionic lipids are not established. In this study, combining magic angle spinning (MAS) solid-state NMR (SSNMR) measurements of isotopically labeled serine headgroups in mixed lipid bilayers with molecular dynamics (MD) simulations of PS lipid bilayers in the presence of different counterions, we provide site-resolved insights into the effects of Ca2+ on the structure and dynamics of lipid bilayers. Ca2+-induced conformational changes of PS in mixed bilayers are observed in both liposomes and Nanodiscs, a nanoscale membrane-mimetic of bilayer patches. Site-resolved multidimensional correlation SSNMR spectra of bilayers containing 13C, 15N-labeled PS demonstrate that Ca2+ ions promote two major PS headgroup conformations, which are well resolved in two-dimensional 13C-13C, 15N-13C and 31P-13C spectra. The results of MD simulations performed on PS lipid bilayers in the presence or absence of Ca2+ provide an atomic view of the conformational effects underlying the observed spectra.
登录
查看更多内容
影响因子：
2.9
作者：
HAUSER, H;PASCHER, I;SUNDELL, S
通讯作者：
SUNDELL, S
DOI：
10.1073/pnas.062565599
发表时间：
2002-05-14
影响因子：
11.1
作者：
Bayburt, TH;Sligar, SG
通讯作者：
Sligar, SG
影响因子：
4.4
作者：
BENNETT, AE;RIENSTRA, CM;GRIFFIN, RG
通讯作者：
GRIFFIN, RG
影响因子：
2.8
作者：
HEDIGER, S;MEIER, BH;ERNST, RR
通讯作者：
ERNST, RR
影响因子：
3.3
作者：
HUSTED, C;MONTEZ, B;OLDFIELD, E
通讯作者：
OLDFIELD, E