@article{40ec1fdc9616446491596884f4208738,
title = "Structural basis for cellobiose dehydrogenase action during oxidative cellulose degradation",
abstract = "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.",
author = "Tan, {Tien Chye} and Daniel Kracher and Rosaria Gandini and Christoph Sygmund and Roman Kittl and Dietmar Haltrich and H{\"a}llberg, {B. Martin} and Roland Ludwig and Christina Divne",
note = "Funding Information: We thank the beamline staff scientists for support during data collection at beamlines I24 and I02 at Diamond Light Source and ID23-1 at ESRF Grenoble. A. Vasella is thanked for providing the CBLM inhibitor. We acknowledge financial support to C.D. from the Swedish Research Council FORMAS (grants N° 2008-495 and N° 2013-1741), the Swedish Research Council VR (grants N° 2008–4056 and N° 2011–5768), and the Carl Tryggers Foundation (N° CTS08:78). B.M.H. acknowledges funding from the Swedish Research Council VR (grant N° 2011–6510). R.L. acknowledges funding from the European Commission Project INDOX (N° FP7-KBBE-2013-7-613549), R.K. acknowledges the Austrian Science Fund (FWF, project N° P25148-B20) and D.K. thanks the Doctoral programme {\textquoteleft}BioToP—Biomolecular Technology of Proteins{\textquoteright} (FWF W1224). The research leading to these results has received funding from the European Community{\textquoteright}s Seventh Framework Programme (FP7/2007–2013) under BioStruct-X (grant agreement N° 283570). The crystallographic work was facilitated by the Protein Science Facility at Karolinska Institutet/SciLifeLab (http://psf.ki.se). The SAXS work was conducted at the Advanced Light Source (ALS), a national user facility operated by Lawrence Berkeley National Laboratory on behalf of the Department of Energy, Office of Basic Energy Sciences, through the Integrated Diffraction Analysis Technologies (IDAT) programme, supported by DOE Office of Biological and Environmental Research, and additional support comes from the National Institute of Health project MINOS (R01GM105404); and at the MAX II SAXS beamline I911-SAXS at MAX IV Laboratory, Lund, Sweden. For automated docking using HADDOCK we acknowledge the use of web portals, computing and storage facilities made available through the WeNMR project (European FP7 e-Infrastructure grant, contract no. 261572, www.wenmr.eu), supported by the European Grid Initiative (EGI) through the national GRID Initiatives of Belgium, France, Italy, Germany, the Netherlands, Poland, Portugal, Spain, UK, South Africa, Malaysia, Taiwan, the Latin America GRID infrastructure via the Gisela project, the International Desktop Grid Federation (IDGF) with its volunteers and the US Open Science Grid (OSG). Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",
year = "2015",
month = jul,
day = "7",
doi = "10.1038/ncomms8542",
language = "English",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}