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

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 post-translational modifications and the unique Ni porphyrin cofactor 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 new targets for the design of MCR inhibitors. One-sentence summaryStructural characterization of methyl-coenzyme M reductase assembly intermediates.