Activator-induced conformational changes regulate division-associated peptidoglycan amidases.
Activator-induced conformational changes regulate division-associated peptidoglycan amidases.
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DOI：
10.1073/pnas.2302580120
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发表时间：
2023-06-13
影响因子：
11.1
通讯作者：
Crow, Allister
中科院分区：
文献类型：
--
作者：
Cook, Jonathan;Baverstock, Tyler C.;McAndrew, Martin B. L.;Roper, David I.;Stansfeld, Phillip J.;Crow, Allister
肽聚糖酰胺酶在细胞分裂过程中破坏肽聚糖层，维持细胞包膜的完整性。在这里，我们展示了一个处于自抑制（“关闭”）状态的分离肽聚糖水解酶的结构，以及与EnvC的激活LytM结构域结合的第二个酰胺酶的结构，显示了活性（“打开”）状态。这些结构的比较提供了重要的分子见解肽聚糖水解酶的激活同源激活剂。AmiA和AmiB是来自大肠杆菌的肽聚糖水解酶，在细菌细胞分裂过程中需要打破肽聚糖层并保持细胞包膜的完整性。在体内，AmiA和AmiB的活性通过它们与膜结合的FtsEX-EnvC复合物的相互作用受到严格控制。AmiA和AmiB的激活需要进入EnvC的酰胺酶激活LytM结构域中的凹槽，该凹槽由atp驱动的ft性- EnvC复合物的构象变化控制。在这里，我们展示了分离的AmiA蛋白的高分辨率结构，证实了它与AmiB和AmiC相同的自抑制方式，以及AmiB酶结构域与激活EnvC LytM结构域结合的复合物。在分离的情况下，AmiA的活性位点被一个自抑制螺旋阻断，该螺旋直接与催化锌结合，并填充预期的容纳肽聚糖结合的体积。在该复合物中，EnvC LytM结构域的结合诱导构象变化，取代酰胺酶自抑制螺旋，重组活性位点。我们的结构，连同互补诱变工作，定义了激活AmiA和/或AmiB所需的构象变化，通过它们与同源激活剂EnvC的相互作用。
Peptidoglycan amidases break the peptidoglycan layer during cell division and maintain integrity of the cell envelope. Here, we present structures of an isolated peptidoglycan hydrolase in an autoinhibited (“off”) state and a second amidase bound to the activating LytM domain of EnvC revealing the active (“on”) state. A comparison of these structures provides important molecular insights into the activation of peptidoglycan hydrolases by their cognate activators. AmiA and AmiB are peptidoglycan-hydrolyzing enzymes from Escherichia coli that are required to break the peptidoglycan layer during bacterial cell division and maintain integrity of the cell envelope. In vivo, the activity of AmiA and AmiB is tightly controlled through their interactions with the membrane-bound FtsEX–EnvC complex. Activation of AmiA and AmiB requires access to a groove in the amidase-activating LytM domain of EnvC which is gated by ATP-driven conformational changes in FtsEX–EnvC complex. Here, we present a high-resolution structure of the isolated AmiA protein, confirming that it is autoinhibited in the same manner as AmiB and AmiC, and a complex of the AmiB enzymatic domain bound to the activating EnvC LytM domain. In isolation, the active site of AmiA is blocked by an autoinhibitory helix that binds directly to the catalytic zinc and fills the volume expected to accommodate peptidoglycan binding. In the complex, binding of the EnvC LytM domain induces a conformational change that displaces the amidase autoinhibitory helix and reorganizes the active site for activity. Our structures, together with complementary mutagenesis work, defines the conformational changes required to activate AmiA and/or AmiB through their interaction with their cognate activator EnvC.
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LOLCDE的冷冻EM结构揭示了大肠杆菌中细菌脂蛋白分选的分子机制。
影响因子：
9.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.1073/pnas.2123385119
发表时间：
2022-07-05
影响因子：
11.1
作者：
通讯作者：
--
影响因子：
5.2
作者：
Greene NP;Kaplan E;Crow A;Koronakis V
通讯作者：
Koronakis V
影响因子：
3.6
作者：
Rocaboy, Mathieu;Herman, Raphael;Kerff, Frederic
通讯作者：
Kerff, Frederic