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首页> 外文期刊>Biochemistry >Bilayer mechanical properties regulate the transmembrane helix mobility and enzymatic state of CD39
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Bilayer mechanical properties regulate the transmembrane helix mobility and enzymatic state of CD39

机译：双层机械性能调节CD39的跨膜螺旋迁移率和酶促状态

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摘要

CD39 can exist in at least two distinct functional states depending on the presence and intact membrane integration of its two transmembrane helices. In native membranes, the transmembrane helices undergo dynamic rotational motions that are required for enzymatic activity and are regulated by substrate binding. In this study, we show that bilayer mechanical properties regulate conversion between the two enzymatic functional states by modulating transmembrane helix dynamics. Alteration of membrane properties by insertion of cone-shaped or inverse cone-shaped amphiphiles or by cholesterol removal switches CD39 to the same enzymatic state that removal or solubilization of the transmembrane domains does. The same membrane alterations increase the propensity of both transmembrane helices to rotate within the packed structure, resulting in a structure with greater mobility but not an altered primary conformation. Membrane alteration also abolishes the ability of the substrate to stabilize the helices in their primary conformation, indicating a loss of coupling between substrate binding and transmembrane helix dynamics. Removal of either transmembrane helix mimics the effect of membrane alteration on the mobility and substrate sensitivity of the remaining helix, suggesting that the ends of the extracellular domain have intrinsic flexibility. We suggest that a mechanical bilayer property, potentially elasticity, regulates CD39 by altering the balance between the stability and flexibility of its transmembrane helices and, in turn, of its active site.
机译：CD39可以以至少两个不同的功能状态存在，这取决于其两个跨膜螺旋的存在和完整的膜整合。在天然膜中，跨膜螺旋经历酶活性所需的动态旋转运动，并受底物结合调节。在这项研究中，我们表明双层机械性能通过调节跨膜螺旋动力学来调节两个酶功能状态之间的转换。通过插入圆锥形或倒圆锥形的两亲物或通过胆固醇去除来改变膜性质，将CD39切换到与跨膜结构域去除或溶解相同的酶状态。相同的膜变化增加了两个跨膜螺旋在堆积结构内旋转的倾向，从而导致结构具有更大的迁移率，但基本构象却没有变化。膜改变也消除了底物将螺旋稳定在其主要构象中的能力，这表明底物结合与跨膜螺旋动力学之间的偶联损失。除去任一跨膜螺旋都模拟了膜改变对其余螺旋的迁移率和底物敏感性的影响，表明细胞外结构域的末端具有固有的柔性。我们建议机械的双层属性，潜在的弹性，通过改变其跨膜螺旋的稳定性和柔韧性以及其活性位点之间的平衡来调节CD39。

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