Architecture of a complete Bce-type antimicrobial peptide resistance module.
Architecture of a complete Bce-type antimicrobial peptide resistance module.
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DOI：
10.1038/s41467-023-39678-w
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发表时间：
2023-07-01
影响因子：
16.6
通讯作者：
Orlando BJ
中科院分区：
文献类型：
--
作者：
George NL;Orlando BJ
革兰氏阳性菌合成并分泌靶向肽聚糖合成的基本过程的抗菌肽。这些抗微生物肽不仅调节微生物群落的动力学，而且具有临床重要性，例如杆菌肽、万古霉素和达托霉素。许多革兰氏阳性菌已经进化出专门的抗菌肽传感和抗性机制，称为Bce模块。这些模块是由一个不寻常的Bce型ABC转运蛋白与双组分系统传感器组氨酸激酶相互作用形成的膜蛋白复合物。在这项工作中，我们提供了第一个结构的见解，这些模块的膜蛋白组分如何组装成一个功能复合物。一个完整的BCE模块的冷冻EM结构揭示了一个意想不到的复杂的组装机制，和传感器组氨酸激酶的广泛的结构灵活性。在不可水解的ATP类似物的存在下的复合物的结构揭示了核苷酸结合如何引发复合物用于随后的激活。伴随的生物化学数据证明了复合物的单个膜蛋白组分如何相互作用以产生严格调节的酶系统。在这里，作者介绍了枯草芽孢杆菌杆菌肽抗性模块BceABS的冷冻EM结构，提供了对复合物内的组装和构象动力学以及单个蛋白质组分之间的协同调节的深入了解。
Gram-positive bacteria synthesize and secrete antimicrobial peptides that target the essential process of peptidoglycan synthesis. These antimicrobial peptides not only regulate the dynamics of microbial communities but are also of clinical importance as exemplified by peptides such as bacitracin, vancomycin, and daptomycin. Many gram-positive species have evolved specialized antimicrobial peptide sensing and resistance machinery known as Bce modules. These modules are membrane protein complexes formed by an unusual Bce-type ABC transporter interacting with a two-component system sensor histidine kinase. In this work, we provide the first structural insight into how the membrane protein components of these modules assemble into a functional complex. A cryo-EM structure of an entire Bce module revealed an unexpected mechanism of complex assembly, and extensive structural flexibility in the sensor histidine kinase. Structures of the complex in the presence of a non-hydrolysable ATP analog reveal how nucleotide binding primes the complex for subsequent activation. Accompanying biochemical data demonstrate how the individual membrane protein components of the complex exert functional control over one another to create a tightly regulated enzymatic system. Here the authors present cryo-EM structures of the Bacillus subtilis bacitracin resistance module BceABS, providing insight into the assembly and conformational dynamics within the complex, and coregulation between individual protein components.
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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：
10.1107/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：
3.6
作者：
Gebhard, Susanne;Mascher, Thorsten
通讯作者：
Mascher, Thorsten
影响因子：
48
作者：
Punjani, Ali;Rubinstein, John L.;Brubaker, Marcus A.
通讯作者：
Brubaker, Marcus A.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH