Flexible and rigid structures in HIV-1 p17 matrix protein monitored by relaxation and amide proton exchange using NMR
Flexible and rigid structures in HIV-1 p17 matrix protein monitored by relaxation and amide proton exchange using NMR
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使用 NMR 通过弛豫和酰胺质子交换监测 HIV-1 p17 基质蛋白的柔性和刚性结构
DOI：
10.1016/j.bbapap.2013.12.010
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
C.*
中科院分区：
文献类型：
--
作者：
Ohori;Y.;Okazaki;H.;Watanabe;S.;Tochio;N.;Arai;M.;Kigawa;T.;and Nishimura;C.*
HIV-1 p17基质蛋白是一种多功能蛋白，可与其他分子（包括蛋白质和膜）相互作用。其折叠和部分未折叠状态之间的动态结构对于相互作用分子的识别至关重要。p17基质蛋白最重要的作用之一是其与Gag多聚蛋白一起定位于质膜。连接到p17基质蛋白N-末端的肉豆蔻基作为与质膜结合的锚发挥作用。生物化学研究表明，有两个区域对它的功能很重要：D14-L31和V84-V88。在这里，p17基质蛋白的动态结构进行了研究，使用核磁共振弛豫和酰胺质子交换实验在生理pH值为7.0。结果表明，α12环，包括14-31区域，是相对灵活的，螺旋4，包括84-88区域，是该蛋白中最受保护的螺旋。然而，在α34-环中靠近螺旋4的残基具有低的序参量和高的酰胺质子交换率，表明高柔性。该区域可能是柔性的，因为该环起到优化螺旋3和4之间的相互作用的铰链的作用。K113-Y132的C-末端长区呈无序结构。此外，由于基于顺序参数的柔性C-末端尾部，C-末端螺旋5似乎略微不稳定。因此，p17基质蛋白的动态结构可能与其多种功能有关。
The HIV-1 p17 matrix protein is a multifunctional protein that interacts with other molecules including proteins and membranes. The dynamic structure between its folded and partially unfolded states can be critical for the recognition of interacting molecules. One of the most important roles of the p17 matrix protein is its localization to the plasma membrane with the Gag polyprotein. The myristyl group attached to the N-terminus on the p17 matrix protein functions as an anchor for binding to the plasma membrane. Biochemical studies revealed that two regions are important for its function: D14–L31 and V84–V88. Here, the dynamic structures of the p17 matrix protein were studied using NMR for relaxation and amide proton exchange experiments at the physiological pH of 7.0. The results revealed that the α12-loop, which includes the 14–31 region, was relatively flexible, and that helix 4, including the 84–88 region, was the most protected helix in this protein. However, the residues in the α34-loop near helix 4 had a low order parameter and high exchange rate of amide protons, indicating high flexibility. This region is probably flexible because this loop functions as a hinge for optimizing the interactions between helices 3 and 4. The C-terminal long region of K113-Y132 adopted a disordered structure. Furthermore, the C-terminal helix 5 appeared to be slightly destabilized due to the flexible C-terminal tail based on the order parameters. Thus, the dynamic structure of the p17 matrix protein may be related to its multiple functions.