MICALs.
MICALs.
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DOI：
10.1016/j.cub.2018.01.025
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发表时间：
2018-05-07
期刊：
影响因子：
--
通讯作者：
Terman JR
中科院分区：
文献类型：
--
作者：
Alto LT;Terman JR
(A)Mical家族蛋白包括果蝇Mical和三种脊椎动物MICAL，Mical-1、-2和-3。所有Mical蛋白都由一个氨基末端氧化还原(Redox)酶切域、一个钙蛋白同源(CH)结构域、一个LIM结构域、一个Src同源3(SH3)结构域、富含脯氨酸的结合基序(PxxP)和一个包含丛蛋白相互作用区(PIR)和Rab结合区(RBD)的羧基末端卷曲螺旋结构域(CC)组成。由于不同的MICAL和每个MICAL的不同蛋白质剪接形式的长度不同，所定义的结构域之间的区域被表示为“可变区”。人类Mical-2的CC结构域上有问号，因为该蛋白的许多标记的cDNA不包括CC结构域，但Mical-2基因组位置包括一个类似于Mical-1和-3的CC编码区。(B)Mical的活动被发现与许多细胞事件有关(如所列出的)，这些事件有助于多种细胞类型的发育和动态平衡，包括神经元。在许多这样的事件中，Mical可以破坏和分解丝状肌动蛋白(F-actin)。(C)目前对Mical功能的模型是，在没有信号的情况下，Mical的氧化还原活性是自动抑制的和不活跃的。Mical通过其CC结构域与丛状受体相互作用，在Semaphorin-Plexin信号转导过程中，Mical的氧化还原域被激活。化学活性也通过与生长因子信号组件和Rab家族蛋白的相互作用来调节。Active Mical结合F-肌动蛋白，并使用NADPH作为辅酶来特异性氧化肌动蛋白D-环(Box)中的蛋氨酸(Mets)44和47。D-环介导肌动蛋白单体/细丝亚基之间的结合，Mical对Met44和Met47的靶向氧化破坏了这些相互作用，导致F-肌动蛋白的分解。已知Cofilin还可以加速Mical-氧化的肌动蛋白的分解，反之亦然。氧化的肌动蛋白被细胞还原酶SelR/MSRB还原，为肌动蛋白动力学的氧化还原调节创造了一个可逆的系统。
(A) MICAL family proteins include Drosophila Mical and three vertebrate MICALs, MICAL-1,-2 and-3. All MICAL proteins consist of an amino-terminal oxidation–reduction (redox) enzymatic domain, a calponin homology (CH) domain, a LIM domain, Src homology 3 (SH3) domain proline-rich binding motifs (PxxP), and a carboxy-terminal coiled coil domain (CC), which contains a Plexin-interacting region (PIR) and a Rab-binding domain (RBD). The regions between defined domains are denoted as ‘variable regions’ because they differ in length for different MICALs and for the different protein splice forms of each MICAL. Question marks are placed over the CC domain for human MICAL-2 because many notated cDNAs for this protein do not include the CC domain, but the MICAL-2 genomic locus includes a CC-coding region similar to MICAL-1 and-3.(B) MICAL activity has been found to be involved in many cellular events (as listed) that contribute to both development and homeostasis in multiple cell types, including neurons. In many of these events, MICAL is known to destabilize and disassemble filamentous actin (F-actin).(C) The current model for MICAL function is that in the absence of signaling, the redox activity of MICAL is autoinhibited and inactive. MICAL interacts with the Plexin receptor through its CC domain, and upon Semaphorin–Plexin signaling, MICAL’s redox domain is activated. MICAL activity is also regulated through interactions with growth factor signaling components and Rab family proteins. Active MICAL binds F-actin and uses NADPH as a coenzyme to specifically oxidize methionines (Mets) 44 and 47 within the D-loop of actin (box). The D-loop mediates binding between actin monomers/filament subunits and MICAL’s targeted oxidation of Met44 and Met47 disrupts these interactions, resulting in F-actin disassembly. Cofilin is also known to accelerate the disassembly of MICAL-oxidized actin, and vice versa. MICAL-oxidized actin is reduced by the cellular reductase SelR/MsrB, creating a reversible system for redox regulation of actin dynamics.
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Micals是从果蝇到人类保守的F-肌动蛋白拆除氧化还原酶的家族。
影响因子：
4.6
作者：
Wu H;Yesilyurt HG;Yoon J;Terman JR
通讯作者：
Terman JR
影响因子：
21.3
作者：
Grintsevich EE;Yesilyurt HG;Rich SK;Hung RJ;Terman JR;Reisler E
通讯作者：
Reisler E
影响因子：
64.8
作者：
Orr BO;Fetter RD;Davis GW
通讯作者：
Davis GW
Mical Link将信号量与F-肌动蛋白拆卸。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
25
作者：
Kirilly, Daniel;Gu, Ying;Yu, Fengwei
通讯作者：
Yu, Fengwei