Mechanism of Structural Tuning of the Hepatitis C Virus Human Cellular Receptor CD81 Large Extracellular Loop

Abstract

(Structure 25, 53–65; January 3, 2017) During the preparation of this paper, Dr. Roversi’s name was omitted from the author list and the Acknowledgements section. The complete author list including Dr. Roversi appears in this Correction and the revised Author Contributions and Acknowledgements sections appear below. The original article has been corrected online. The authors regret this error and apologize for any confusion that it has caused. N.G.A.A. conceived and coordinated the study. E.S.C., A.L.R., P.R., and N.G.A.A. performed biophysical experiments, collected and processed X-ray data, and determined the crystal structures. N.G.A.A. and A.L.R. performed the structure refinement. E.S.C., N.G.A.A., P.S., and M.O. designed the molecular modeling study. P.S., A.H., and M.O. performed molecular simulations. All authors analyzed and interpreted the data. E.S.C., P.S., and N.G.A.A. wrote the manuscript with contributions from all authors, who approved the final version. We are grateful to Radu Aricescu (Oxford University) for supplying the pHLSec vector and for useful suggestions on mammalian protein expression, to Magdalena Wojtas (CIC bioGUNE) for assisting in cloning CD81LEL, and to Marina Ondiviela and Diego Charro (CIC bioGUNE) for protein production. Marina Ondiviela is thanked for expert help in cloning and protein purification. We also thank Hani Boshra (CIC bioGUNE) for discussion and critical reading of the manuscript. We acknowledge the Diamond Light Source and the European Synchrotron Radiation Facility (ESRF, France) for provision of synchrotron facilities and the staff at the beamlines I02/I03 at Diamond Light Source (UK) and ID-29/ID23-1 at the ESRF (France) for assistance during data collection. This work was funded by the Spanish Ministerio de Economía y Competitividad (BFU2014-52864-R), by the Catalan SGR, and by the BioExcel and Excellerate EU projects to M.O, by the “la Caixa” PhD program to P.S., and by the Spanish Ministerio de Economia y Competitividad ( BFU2012-33947 and BFU2015-64541-R ) to N.G.A.A. P.R. was a recipient of the Basque Foundation for Science Visiting Fellowship 2012. M.O. is an ICREA Academia Fellow. The research leading to these results has received funding from the European Community's Seventh Framework Programme ( FP7/2007-2013 ) under BioStruct-X (grant agreement no. 283570). Mechanism of Structural Tuning of the Hepatitis C Virus Human Cellular Receptor CD81 Large Extracellular LoopCunha et al.StructureDecember 1, 2016In BriefCD81 is one of the cellular receptors of hepatitis C virus. Here, combining crystallographic and molecular dynamics studies of CD81LEL long-extracellular-loop, Cunha et al. show that its flexibility is an inherent molecular property likely to be tuned by variation in pH and redox conditions. This tuning mechanism would explain the priming role ascribed to CD81LEL in rendering the virus-receptor complex fusogenic during cell entry. Full-Text PDF Open Archive