Properdin oligomers adopt rigid extended conformations supporting function
- Aarhus University, Denmark
- University of Copenhagen, Denmark
- Aarhus Univdersity, Denmark
Abstract
Properdin stabilizes convertases formed upon activation of the complement cascade within the immune system. The biological activity of properdin depends on the oligomerization state, but whether properdin oligomers are rigid and how their structure links to function remains unknown. We show by combining electron microscopy and solution scattering, that properdin oligomers adopt extended rigid and well-defined conformations that are well approximated by single models of apparent n-fold rotational symmetry with dimensions of 230-360 Å. Properdin monomers are pretzel shaped molecules with limited flexibility. In solution, properdin dimers are curved molecules whereas trimers and tetramers are close to being planar molecules. Structural analysis indicates that simultaneous binding through all binding sites to surface linked convertases is unlikely for properdin trimer and tetramers. We show that multivalency alone is insufficient for full activity in a cell lysis assay. Hence, the observed rigid extended oligomer structure is an integral component of properdin function.
Data availability
Scattering data and model for the FP E244K monomer is available as SASBDB entry SASDB69. Scattering data and models for the wild type oligomers are available at SASBDB as entries SASDKA4 (FP2), SASDKB4 (FP3) and SASDKC4 (FP4).
Article and author information
Author details
Kresten Lindorff-Larsen
Gregers R Andersen
Funding
Lundbeckfonden (R155-2015-2666)
- Dennis V Pedersen
- Martin N Pedersen
- Sofia M Mazarakis
- Yong Wang
- Kresten Lindorff-Larsen
- Lise Arleth
- Gregers R Andersen
Novo Nordisk Fonden (NNF16OC0022058)
- Dennis V Pedersen
- Sofia M Mazarakis
- Gregers R Andersen
Novo Nordisk Fonden (NF18OC0032608)
- Kresten Lindorff-Larsen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Pedersen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Properdin oligomers adopt rigid extended conformations supporting function
eLife 10:e63356.
https://doi.org/10.7554/eLife.63356
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