Cholesterol Alters the Orientation and Activity of the Influenza Virus M2 Amphipathic Helix in the Membrane.
Cholesterol Alters the Orientation and Activity of the Influenza Virus M2 Amphipathic Helix in the Membrane.
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DOI：
10.1021/acs.jpcb.0c03331
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发表时间：
2020-08-06
期刊：
影响因子：
--
通讯作者：
Rossman JS
中科院分区：
文献类型：
--
作者：
Martyna A;Bahsoun B;Madsen JJ;Jackson FSJS;Badham MD;Voth GA;Rossman JS
流感病毒M2两亲性螺旋（M2 AH）以胆固醇依赖性方式改变膜曲率，在流感病毒出芽期间介导病毒膜断裂。在这里，我们研究了胆固醇对M2 AH肽操纵膜特性的能力的生物物理效应。我们发现，M2 AH与膜相互作用并形成α-螺旋的能力与膜胆固醇浓度无关;然而，胆固醇影响膜内M2 AH肽的角度。膜取向的这种变化影响M2 AH改变脂质顺序的能力。在低胆固醇膜中，M2 AH被插入到脂质头部基团的水平附近，增加脂质顺序，这可能有助于膜曲率的产生。随着胆固醇含量的增加，M2 AH插入变得更平坦，并且在脂质头基下方的膜中略深，其中极性面可以继续与头基相互作用，而疏水面结合胆固醇。这种改变的取向使脂质堆积缺陷和脂质顺序变化最小化，可能减少膜曲率的产生。因此，胆固醇通过精确调节M2 AH在膜内的定位来调节M2膜断裂。这对理解在特定脂质环境中发生的许多两亲性螺旋驱动的细胞出芽过程具有影响。
The influenza virus M2 amphipathic helix (M2AH) alters membrane curvature in a cholesterol-dependent manner, mediating viral membrane scission during influenza virus budding. Here, we have investigated the biophysical effects of cholesterol on the ability of an M2AH peptide to manipulate membrane properties. We see that the ability of the M2AH to interact with membranes and form an α-helix is independent of membrane cholesterol concentration; however, cholesterol affects the angle of the M2AH peptide within the membrane. This change in membrane orientation affects the ability of the M2AH to alter lipid order. In low-cholesterol membranes, the M2AH is inserted near the level of the lipid head groups, increasing lipid order, which may contribute to generation of the membrane curvature. As the cholesterol content increases, the M2AH insertion becomes flatter and slightly deeper in the membrane below the lipid headgroups, where the polar face can continue to interact with the headgroups while the hydrophobic face binds cholesterol. This changed orientation minimizes lipid packing defects and lipid order changes, likely reducing the generation of membrane curvature. Thus, cholesterol regulates M2 membrane scission by precisely modulating M2AH positioning within the membrane. This has implications for the understanding of many of amphipathic-helix-driven cellular budding processes that occur in specific lipid environments.
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影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
DOI：
10.1002/prot.340230412
发表时间：
1995-12-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Frishman, D;Argos, P
通讯作者：
Argos, P
影响因子：
5.8
作者：
Gautier, Romain;Douguet, Dominique;Drin, Guillaume
通讯作者：
Drin, Guillaume
影响因子：
2.9
作者：
HOOVER, WG
通讯作者：
HOOVER, WG
影响因子：
5.5
作者：
Hess, Berk
通讯作者：
Hess, Berk