Melanophilin Stimulates Myosin-5a Motor Function by Allosterically Inhibiting the Interaction between the Head and Tail of Myosin-5a.
Melanophilin Stimulates Myosin-5a Motor Function by Allosterically Inhibiting the Interaction between the Head and Tail of Myosin-5a.
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亲黑素通过变构抑制肌球蛋白 5a 头部和尾部之间的相互作用来刺激肌球蛋白 5a 运动功能
DOI：
10.1038/srep10874
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发表时间：
2015-06-03
影响因子：
4.6
通讯作者：
Li XD
中科院分区：
文献类型：
--
作者：
Yao LL;Cao QJ;Zhang HM;Zhang J;Cao Y;Li XD
尾部抑制模型被普遍认为是肌球蛋白-5a运动功能的调节模型。被抑制的肌球蛋白-5a是一种折叠构象，其球状尾区(GTD)与其头部相互作用，抑制其运动功能，高钙或货物结合可能减少GTD与肌球蛋白-5a头部之间的相互作用，从而激活运动活动。虽然已经确定肌球蛋白-5a的运动功能受钙离子的调节，但对货物结合的影响知之甚少。我们曾报道亲黑素(MLPH)是一种肌球蛋白-5a结合蛋白，能够激活肌球蛋白-5a的运动功能。在此，我们报道了MLPH的26个氨基酸组成的多肽MLPH-GTBDP足以激活肌球蛋白-5a的运动功能。我们证明MLPH-GTBDP取消了肌球蛋白-5a头部和GTD之间的相互作用，从而诱导了肌球蛋白-5a从折叠到延伸的构象转变，并激活了它的运动功能。GTD的突变表明，GTD使用两个不同的、不重叠的区域与MLPH-GTBDP和肌球蛋白-5a的头部相互作用。我们认为GTD是一种变构蛋白，MLPH变构抑制GTD与肌球蛋白-5a头部之间的相互作用，从而激活肌球蛋白-5a的运动功能。
The tail-inhibition model is generally accepted for the regulation of myosin-5a motor function. Inhibited myosin-5a is in a folded conformation in which its globular tail domain (GTD) interacts with its head and inhibits its motor function and high Ca2+or cargo binding may reduce the interaction between the GTD and the head of myosin-5a, thus activating motor activity. Although it is well established that myosin-5a motor function is regulated by Ca2+, little is known about the effects of cargo binding. We previously reported that melanophilin (Mlph), a myosin-5a cargo-binding protein, is capable of activating myosin-5a motor function. Here, we report that Mlph-GTBDP, a 26 amino-acid-long peptide of Mlph, is sufficient for activating myosin-5a motor function. We demonstrate that Mlph-GTBDP abolishes the interaction between the head and GTD of myosin-5a, thereby inducing a folded-to-extended conformation transition for myosin-5a and activating its motor function. Mutagenesis of the GTD shows that the GTD uses two distinct, non-overlapping regions to interact with Mlph-GTBDP and the head of myosin-5a. We propose that the GTD is an allosteric protein and that Mlph allosterically inhibits the interaction between the GTD and head of myosin-5a, thereby activating myosin-5a motor function.
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影响因子：
64.5
作者：
CHENEY, RE;OSHEA, MK;MOOSEKER, MS
通讯作者：
MOOSEKER, MS
影响因子：
3.3
作者：
Berg, JS;Powell, BC;Cheney, RE
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Cheney, RE
影响因子：
4.8
作者：
Fukuda, M;Kuroda, TS;Mikoshiba, K
通讯作者：
Mikoshiba, K
影响因子：
4.8
作者：
Geething, Nathan C.;Spudich, James A.
通讯作者：
Spudich, James A.
影响因子：
4.8
作者：
Sckolnick, Maria;Krementsova, Elena B.;Trybus, Kathleen M.
通讯作者：
Trybus, Kathleen M.