Head-to-tail interaction between amphotericin B and ergosterol occurs in hydrated phospholipid membrane.
Head-to-tail interaction between amphotericin B and ergosterol occurs in hydrated phospholipid membrane.
复制标题
两性霉素 B 和麦角甾醇之间的头尾相互作用发生在水合磷脂膜中。
作者：
Yuichi Umegawa;Y. Nakagawa;K. Tahara;H. Tsuchikawa;N. Matsumori;T. Oishi;M. Murata
两性霉素B（AmB）被认为是通过在麦角固醇存在下形成离子通道组装体来发挥其抗真菌活性。在本研究中，我们的目的是阐明使用旋转回波双共振（REDOR）光谱的水合磷脂双层中的分子间相互作用的AmB和麦角甾醇的模式。我们首先用C14-（19）F-标记的AmB和生物合成的（13）C-标记的麦角甾醇进行了（13）C{（19）F}REDOR实验，并暗示AmB-麦角甾醇在双层中的相互作用存在“头对头”和“头对尾”取向。为了进一步确认“头-尾”配对，合成了（13）二甲基末端（C26/C27）的C-标记麦角甾醇，并进行了REDOR测量。光谱明确地证明了AmB-麦角固醇配对的“头-尾”取向的存在。为了获得关于麦角甾醇二甲基末端在膜中的位置的信息，使用标记的麦角甾醇和POPC头基的磷原子进行（13）C{（31）P}REDOR。在存在AmB的情况下，在麦角固醇的C26/C27信号处观察到显著的REDOR失相，但在不存在AmB的情况下没有，清楚地表明AmB复合物中麦角固醇的侧链末端接近双层表面。
Amphotericin B (AmB) is thought to exert its antifungal activity by forming an ion-channel assembly in the presence of ergosterol. In the present study we aimed to elucidate the mode of molecular interactions between AmB and ergosterol in hydrated phospholipid bilayers using the rotational echo double resonance (REDOR) spectra. We first performed (13)C{(19)F}REDOR experiments with C14-(19)F-labeled AmB and biosynthetically (13)C-labeled ergosterol and implied that both "head-to-head" and "head-to-tail" orientations occur for AmB-ergosterol interaction in the bilayers. To further confirm the "head-to-tail" pairing, (13)C-labeled ergosterol at the dimethyl terminus (C26/C27) was synthesized and subjected to the REDOR measurements. The spectra unambiguously demonstrated the presence of a "head-to-tail" orientation for AmB-ergosterol pairing. In order to obtain information on the position of the dimethyl terminus of ergosterol in membrane, (13)C{(31)P}REDOR were carried out using the labeled ergosterol and the phosphorus atom of a POPC headgroup. Significant REDOR dephasing was observed at the C26/C27 signal of ergosterol in the presence of AmB, but not in the absence of AmB, clearly indicating that the side-chain terminus of ergosterol in the AmB complex comes close to the bilayer surface.
影响因子：
15
作者：
Palacios, Daniel S.;Anderson, Thomas M.;Burke, Martin D.
通讯作者：
Burke, Martin D.
两性霉素 B 和菲律宾素与甾醇的关联率。
DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Clejan,S;Bittman,R
通讯作者：
Bittman,R