Structural basis for cellobiose dehydrogenase action during oxidative cellulose degradation.

Tan TC, Kracher D, Gandini R, Sygmund C, Kittl R, Haltrich D, Hällberg BM, Ludwig R, Divne C

Nat Commun 6 (-) 7542 [2015-07-07; online 2015-07-07]

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.

Protein Science Facility (PSF)

QC bibliography QC xrefs

PubMed 26151670

DOI 10.1038/ncomms8542

Crossref 10.1038/ncomms8542

PDB 4QI3

PDB 4QI4

PDB 4QI5

PDB 4QI6

PDB 4QI7

PDB 4QI8

ncomms8542

pmc PMC4507011