McrD binds asymmetrically to methyl-coenzyme M reductase improving active-site accessibility during assembly

  1. Grayson L. Chadwick
  2. Aaron M. N. Joiner
  3. Sangeetha Ramesh
  4. Douglas A. Mitchell
  5. Dipti D. Nayak

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Abstract

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 F 430 . 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 F 430 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 F 430 —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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  1. Version published to 10.1073/pnas.2302815120
  2. Arcadia Science

    This is a really interesting and rigorous work structurally characterizing the Mcr complex and the role of McrD. Its really impressive that you purified the complex from the native system. Congrats and good work! A few questions:

    I found it striking that McrD was not essential for Mcr complex formation, despite being so well conserved.

    1. Does McrD have any recognizable domains or folds that could tell you about how it might be participating in Mcr complex biogenesis? Can this tell you anything about its specific evolutionary history or mechanism of action?

    2. Is McrD found in organisms that don't have the other pathway members? If so, what other cellular processes could it be involved in?

  3. Arcadia Science

    This is a really interesting and rigorous work structurally characterizing the Mcr complex and the role of McrD. Its really impressive that you purified the complex from the native system. Congrats and good work! A few questions:

    I found it striking that McrD was not essential for Mcr complex formation, despite being so well conserved.

    1. Does McrD have any recognizable domains or folds that could tell you about how it might be participating in Mcr complex biogenesis? Can this tell you anything about its specific evolutionary history or mechanism of action?

    2. Is McrD found in organisms that don't have the other pathway members? If so, what other cellular processes could it be involved in?

  4. Version published to 10.1101/2023.02.01.526716v1 on bioRxiv