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Structural basis for cellobiose dehydrogenase action during oxidative cellulose degradation
KTH, School of Biotechnology (BIO), Industrial Biotechnology.
KTH, School of Biotechnology (BIO), Industrial Biotechnology.
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2015 (English)In: Nature communications, Vol. 6, 7542-7542 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2015. Vol. 6, 7542-7542 p.
National Category
Industrial Biotechnology
URN: urn:nbn:se:kth:diva-171174DOI: 10.1038/ncomms8542ISI: 000358852700001PubMedID: 26151670ScopusID: 2-s2.0-84936851753OAI: diva2:842371
Swedish Research Council Formas, 2008-495Swedish Research Council Formas, 2013-1741Swedish Research Council, 2008-4056Swedish Research Council, 2011-5768Swedish Research Council, 2011-6510Carl Tryggers foundation , CTS08:78EU, FP7, Seventh Framework Programme, FP7-KBBE-2013-7-613549

QC 20150720

Available from: 2015-07-20 Created: 2015-07-20 Last updated: 2015-09-10Bibliographically approved

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