Article abstract
Nature Immunology 9, 753 - 760 (2008)
Published online: 8 June 2008 | Corrected online: 20 June 2008 | doi:10.1038/ni.1625
There is an Erratum (August 2008) associated with this Article.
Structure of and influence of a tick complement inhibitor on human complement component 5
Folmer Fredslund1, Nick S Laursen1, Pietro Roversi2, Lasse Jenner1,7, Cristiano L P Oliveira3,4, Jan S Pedersen3,4, Miles A Nunn5, Susan M Lea2, Richard Discipio6, Lars Sottrup-Jensen1 & Gregers R Andersen1,4
Abstract
To provide insight into the structural and functional properties of human complement component 5 (C5), we determined its crystal structure at a resolution of 3.1 Å. The core of C5 adopted a structure resembling that of C3, with the domain arrangement at the position corresponding to the C3 thioester being very well conserved. However, in contrast to C3, the convertase cleavage site in C5 was ordered and the C345C domain flexibly attached to the core of C5. Binding of the tick C5 inhibitor OmCI to C5 resulted in stabilization of the global conformation of C5 but did not block the convertase cleavage site. The structure of C5 may render possible a structure-based approach for the design of new selective complement inhibitors.
- Department of Molecular Biology, University of Aarhus, DK-8000 Aarhus, Denmark.
- Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3ER, UK.
- Department of Chemistry, University of Aarhus, DK-8000 Aarhus, Denmark.
- Centre for mRNP Biogenesis and Metabolism, University of Aarhus, Denmark.
- Centre for Ecology and Hydrology Oxford, Oxford OX1 3SR, UK.
- La Jolla Institute for Experimental Medicine, 505 Coast Boulevard S., La Jolla, California 92037, USA.
- Present address: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67404, France.
Correspondence to: Gregers R Andersen1,4 e-mail: gra@mb.au.dk
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