Molecular details of α-synuclein membrane association revealed by neutrons and photons.
Molecular details of α-synuclein membrane association revealed by neutrons and photons.
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DOI：
10.1021/jp512499r
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发表时间：
2015-04-09
期刊：
影响因子：
--
通讯作者：
Lee JC
中科院分区：
文献类型：
--
作者：
Jiang Z;Hess SK;Heinrich F;Lee JC
α-突触核蛋白（α-syn）是一种与帕金森病相关的丰富的神经元蛋白，在溶液中无序，但在带负电荷的膜上以弯曲螺旋和细长螺旋之间的平衡存在。本文采用中子反射法（NR）和荧光光谱法揭示了α-syn与两种阴离子脂质磷脂酸（PA）和磷脂酰丝氨酸（PS）相互作用的分子细节。NR和位点特异性色氨酸测量表明，尽管α-syn更倾向于与PA结合，但α-syn在PA-或ps -含膜（~ 9-11 Å）上的穿透深度相似。然而，通过溴化脂质对单个色氨酸猝灭谱的更仔细检查，发现了局部膜相互作用的差异，特别是在39号位置，在那里观察到构象异质性。数据还表明，虽然W94穿透双分子层的深度与W4一样，但W94位于更极性的周围。综上所述，我们认为位置4和94附近的N端和c端区域锚定在膜上，而假设的连接子跨越残基39具有多种构象，这些构象对膜表面的化学性质很敏感。这种灵活性可能使α-syn能够在体内结合多种生物膜。
α-Synuclein (α-syn) is an abundant neuronal protein associated with Parkinson’s disease that is disordered in solution, but exists in equilibrium between a bent- and an elongated-helix on negatively charged membranes. Here, neutron reflectometry (NR) and fluorescence spectroscopy were employed to uncover molecular details of the interaction between α-syn and two anionic lipids, phosphatidic acid (PA) and phosphatidylserine (PS). Both NR and site-specific Trp measurements indicate that penetration depth of α-syn is similar for either PA- or PS-containing membranes (~9–11 Å from bilayer center) even though there is a preference for α-syn binding to PA. However, closer examination of the individual Trp quenching profiles by brominated lipids reveal differences into local membrane interactions especially at position 39 where conformational heterogeneity was observed. The data also indicate that while W94 penetrates the bilayer as deeply as W4, W94 resides in a more polar surrounding. Taken together, we suggest the N- and C-terminal regions near positions 4 and 94 are anchored to the membrane, while the putative linker spanning residue 39 samples multiple conformations, which are sensitive to the chemical nature of the membrane surface. This flexibility may enable α-syn to bind diverse biomembranes in vivo.
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影响因子：
8.6
作者：
Appel-Cresswell, Silke;Vilarino-Guell, Carles;Farrer, Matthew J.
通讯作者：
Farrer, Matthew J.
DOI：
10.1021/la401132c
发表时间：
2013-07-09
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
--
作者：
Budvytyte R;Valincius G;Niaura G;Voiciuk V;Mickevicius M;Chapman H;Goh HZ;Shekhar P;Heinrich F;Shenoy S;Lösche M;Vanderah DJ
通讯作者：
Vanderah DJ
影响因子：
15.1
作者：
Danzer KM;Kranich LR;Ruf WP;Cagsal-Getkin O;Winslow AR;Zhu L;Vanderburg CR;McLean PJ
通讯作者：
McLean PJ
影响因子：
64.8
作者：
通讯作者：
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影响因子：
3.4
作者：
Bartels, Tim;Ahlstrom, Logan S.;Beyer, Klaus
通讯作者：
Beyer, Klaus