McrD binds asymmetrically to methyl-coenzyme M reductase improving active-site accessibility during assembly.
McrD binds asymmetrically to methyl-coenzyme M reductase improving active-site accessibility during assembly.
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DOI：
10.1073/pnas.2302815120
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发表时间：
2023-06-20
影响因子：
11.1
通讯作者：
Nayak, Dipti D.
中科院分区：
文献类型：
--
作者：
Chadwick, Grayson L.;Joiner, Aaron M. N.;Ramesh, Sangeetha;Mitchell, Douglas A.;Nayak, Dipti D.
甲烷是气候变化的第二大贡献者，其变暖潜力远远大于二氧化碳。减少甲烷排放对于实现气候目标至关重要。甲烷的很大一部分来自产甲烷古菌，通过一种叫做甲基辅酶M还原酶（MCR）的酶的作用。通过抑制MCR的组装或活性，可以大幅减少甲烷排放。在这里，我们提供了一个模型产甲烷菌，醋酸甲烷八叠球菌MCR组件的机制一瞥。我们发现，McrD，一个普遍保守的蛋白质产甲烷菌，促进插入F430，一个含镍的四吡咯MCR用于催化。最终，这些见解将促进转化研究，为全球甲烷减排设计强有力的措施。甲基辅酶M还原酶（MCR）催化甲烷的形成，其活性几乎占所有生物产生的甲烷释放到大气中。MCR的组装是一个复杂的过程，涉及安装一组复杂的翻译后修饰和独特的含镍四吡咯称为辅酶F430。尽管经过了数十年的研究，MCR组装的细节在很大程度上仍然没有得到解决。在这里，我们报告的结构表征MCR在两个中间状态的组装。这些中间状态缺乏一种或两种F430辅因子，并与之前未表征的McrD蛋白形成复合物。发现McrD不对称地与MCR结合，置换α亚基的大区域，并增加F430安装的活性位点可及性，从而阐明MCR组装和McrD在其中的作用。这项工作为MCR在异源宿主中的表达提供了重要信息，并为MCR抑制剂的设计提供了靶点。
Methane is the second largest contributor to climate change with a warming potential substantially greater than carbon dioxide. Reducing methane emissions is crucial to meet climate goals. A significant portion of methane comes from methanogenic archaea through the action of an enzyme called methyl-coenzyme M reductase (MCR). Methane emissions can be drastically reduced by inhibiting the assembly or activity of MCR. Here, we provide a glimpse into the mechanism of MCR assembly in the model methanogen, Methanosarcina acetivorans. We show that McrD, a universally conserved protein in methanogens, facilitates the insertion of F430, a Ni-containing tetrapyrrole used by MCR for catalysis. Ultimately, these insights will facilitate translational research to design robust measures for global methane mitigation. Methyl-coenzyme M reductase (MCR) catalyzes the formation of methane, and its activity accounts for nearly all biologically produced methane released into the atmosphere. The assembly of MCR is an intricate process involving the installation of a complex set of posttranslational modifications and the unique Ni-containing tetrapyrrole called coenzyme F430. Despite decades of research, details of MCR assembly remain largely unresolved. Here, we report the structural characterization of MCR in two intermediate states of assembly. These intermediate states lack one or both F430 cofactors and form complexes with the previously uncharacterized McrD protein. McrD is found to bind asymmetrically to MCR, displacing large regions of the alpha subunit and increasing active-site accessibility for the installation of F430—shedding light on the assembly of MCR and the role of McrD therein. This work offers crucial information for the expression of MCR in a heterologous host and provides targets for the design of MCR inhibitors.
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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：
10.1073/pnas.1618596114
发表时间：
2017-03-14
影响因子：
11.1
作者：
Nayak, Dipti D.;Metcalf, William W.
通讯作者：
Metcalf, William W.
影响因子：
64.8
作者：
Shima, Seigo;Krueger, Martin;Ermler, Ulrich
通讯作者：
Ermler, Ulrich
影响因子：
56.9
作者：
Ermler, U;Grabarse, W;Thauer, RK
通讯作者：
Thauer, RK
影响因子：
9.8
作者：
Nayak, Dipti D.;Liu, Andi;Metcalf, William W.
通讯作者：
Metcalf, William W.