Abstract
Secondary structure refolding is a key event in biology as it modulates the conformation of many proteins in the cell, generating functional or aberrant states. The crystal structures of mannosyltransferase PimA reveal an exceptional flexibility of the protein along the catalytic cycle, including β-strand–to–α-helix and α-helix–to–β-strand transitions. These structural changes modulate catalysis and are promoted by interactions of the protein with anionic phospholipids in the membrane.
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Acknowledgements
We acknowledge A. Haouz and P. Weber (Institut Pasteur, France) for help with robotic crystallization; S. Lopez Fernandez and P. Arrasate (Structural Glycobiology Group, Unit of Biophysics, Spain) for technical assistance; and the European Synchrotron Radiation Facility (ESRF), the French National Synchrotron SOLEIL, the Diamond Light Source (DLS) and the Swiss Light Source (SLS) for granting access to synchrotron radiation facilities and their staff for the onsite assistance. We specially thank the BioStruct-X project to support access to structural biology facilities. Technical support provided by Universidad del País Vasco/Euskal Herriko Unibertsitatea and Ministerio de Ciencia e Innovación is acknowledged. We also thank all members of the Structural Glycobiology Group for valuable scientific discussions. This work was supported by the European Community's Sixth and Seventh Framework Programmes (contracts LSHP-CT-2005-018923 and HEALTH-F3-2011-260872), the Institut Pasteur, the Spanish Ministry of Science and Innovation (contracts SAF2010-19096 and BIO2013-49022-C2-2-R), IKERBASQUE, the Basque Foundation for Science, the Basque Government and the Fundación Biofísica Bizkaia.
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M.E.G. and P.M.A. conceived the project. D.G., D.A.-J. and M.B. performed the crystallographic studies. S.U., A.R.-U., M.A.M., N.B. and N.C. prepared and characterized wild-type PimA and the different mutants. D.G., M.A.M., M.B., A.C., M.E.G. & P.M.A. analyzed the results. D.G., A.C., M.E.G. & P.M.A. wrote the manuscript.
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Supplementary Text and Figures
Supplementary Results, Supplementary Figures 1–15 and Supplementary Table 1. (PDF 2845 kb)
Supplementary Video 1
Structural transition between the extended and compact conformational states of apo PimA (MPG 522 kb)
Supplementary Video 2
Structural transition between apo PimA and GDP-bound PimA involving the reshuffling of secondary structural elements from the N-terminal domain. (MPG 1520 kb)
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Giganti, D., Albesa-Jové, D., Urresti, S. et al. Secondary structure reshuffling modulates glycosyltransferase function at the membrane. Nat Chem Biol 11, 16–18 (2015). https://doi.org/10.1038/nchembio.1694
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DOI: https://doi.org/10.1038/nchembio.1694
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