A new paradigm for cellulose depolymerization by fungi focuses on an oxidative mechanism involving cellobiose dehydrogenases (CDH) and copper-dependent lytic polysaccharide monooxygenases (LPMO); however, mechanistic studies have been hampered by the lack of structural information regarding CDH. CDH contains a haem-binding cytochrome (CYT) connected via a flexible linker to a flavin-dependent dehydrogenase (DH). Electrons are generated from cellobiose oxidation catalysed by DH and shuttled via CYT to LPMO. Here we present structural analyses that provide a comprehensive picture of CDH conformers, which govern the electron transfer between redox centres. Using structure-based site-directed mutagenesis, rapid kinetics analysis and molecular docking, we demonstrate that flavin-to-haem interdomain electron transfer (IET) is enabled by a haem propionate group and that rapid IET requires a closed CDH state in which the propionate is tightly enfolded by DH. Following haem reduction, CYT reduces LPMO to initiate oxygen activation at the copper centre and subsequent cellulose depolymerization.
Background: The operon structure of the C. elegans genome was used to identify functional interaction partners for the chloride channel ICln.Results: Human ICln and HSPC038 functionally interact, and this interaction between the two proteins was also identified on a molecular level.Conclusion: The functional interaction between ICln and HSPC038 modulates the regulation of the cellular volume.Significance: The operon structure of the C. elegans genome can be used to identify unknown interaction partners including those of membrane proteins, and the summarized experiments provide further insight into the interactome of the connector hub ICln.
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