Secondary-structure switch regulates the substrate binding of a YopJ family acetyltransferase.
Secondary-structure switch regulates the substrate binding of a YopJ family acetyltransferase.
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二级结构开关调节 YopJ 家族乙酰转移酶的底物结合
DOI：
10.1038/s41467-021-26183-1
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发表时间：
2021-10-13
影响因子：
16.6
通讯作者：
Zhang ZM
中科院分区：
文献类型：
--
作者：
Xia Y;Zou R;Escouboué M;Zhong L;Zhu C;Pouzet C;Wu X;Wang Y;Lv G;Zhou H;Sun P;Ding K;Deslandes L;Yuan S;Zhang ZM
耶尔森氏菌外蛋白J（YopJ）家族效应子通过植物和动物病原体的III型分泌系统被广泛部署。作为非典型的乙酰转移酶，YopJ家族效应子的酶活性被真核生物特异性配体肌醇六磷酸（InsP 6）变构激活。然而，基础的分子机制仍然不确定。在这里，我们提出的晶体结构的载脂蛋白PopP 2，YopJ家族成员分泌的植物病原体青枯菌。载脂蛋白PopP 2与InsP 6结合PopP 2的结构比较揭示了以底物结合位点为中心的大量构象重新调整。结合生物化学和计算分析，我们进一步确定了InsP 6与PopP 2的缔合诱导催化核心中的α-螺旋到β-链转变的机制，从而导致靶蛋白结合位点中底物识别螺旋的稳定。总之，我们的研究揭示了InsP 6介导的YopJ家族乙酰转移酶变构调控的分子基础，并进一步扩展了折叠开关蛋白的范式。
The Yersinia outer protein J (YopJ) family effectors are widely deployed through the type III secretion system by both plant and animal pathogens. As non-canonical acetyltransferases, the enzymatic activities of YopJ family effectors are allosterically activated by the eukaryote-specific ligand inositol hexaphosphate (InsP6). However, the underpinning molecular mechanism remains undefined. Here we present the crystal structure of apo-PopP2, a YopJ family member secreted by the plant pathogenRalstonia solanacearum. Structural comparison of apo-PopP2 with the InsP6-bound PopP2 reveals a substantial conformational readjustment centered in the substrate-binding site. Combining biochemical and computational analyses, we further identify a mechanism by which the association of InsP6 with PopP2 induces an α-helix-to-β-strand transition in the catalytic core, resulting in stabilization of the substrate recognition helix in the target protein binding site. Together, our study uncovers the molecular basis governing InsP6-mediated allosteric regulation of YopJ family acetyltransferases and further expands the paradigm of fold-switching proteins.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
14.8
作者：
Giganti, David;Albesa-Jove, David;Alzari, Pedro M.
通讯作者：
Alzari, Pedro M.
DOI：
10.1107/s0907444902016657
发表时间：
2002-11-01
影响因子：
2.2
作者：
Adams, PD;Grosse-Kunstleve, RW;Terwilliger, TC
通讯作者：
Terwilliger, TC
影响因子：
2.9
作者：
Labriola, Jonathan M.;Zhou, Yifan;Nagar, Bhushan
通讯作者：
Nagar, Bhushan
影响因子：
--
作者：
Blind, Raymond D.
通讯作者：
Blind, Raymond D.