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Properdin oligomers adopt rigid extended conformations supporting function
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 combi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857727/ https://www.ncbi.nlm.nih.gov/pubmed/33480354 http://dx.doi.org/10.7554/eLife.63356 |
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author | Pedersen, Dennis V Pedersen, Martin Nors Mazarakis, Sofia MM Wang, Yong Lindorff-Larsen, Kresten Arleth, Lise Andersen, Gregers R |
author_facet | Pedersen, Dennis V Pedersen, Martin Nors Mazarakis, Sofia MM Wang, Yong Lindorff-Larsen, Kresten Arleth, Lise Andersen, Gregers R |
author_sort | Pedersen, Dennis V |
collection | PubMed |
description | 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 which 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. |
format | Online Article Text |
id | pubmed-7857727 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-78577272021-02-04 Properdin oligomers adopt rigid extended conformations supporting function Pedersen, Dennis V Pedersen, Martin Nors Mazarakis, Sofia MM Wang, Yong Lindorff-Larsen, Kresten Arleth, Lise Andersen, Gregers R eLife Immunology and Inflammation 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 which 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. eLife Sciences Publications, Ltd 2021-01-22 /pmc/articles/PMC7857727/ /pubmed/33480354 http://dx.doi.org/10.7554/eLife.63356 Text en © 2021, Pedersen et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Pedersen, Dennis V Pedersen, Martin Nors Mazarakis, Sofia MM Wang, Yong Lindorff-Larsen, Kresten Arleth, Lise Andersen, Gregers R Properdin oligomers adopt rigid extended conformations supporting function |
title | Properdin oligomers adopt rigid extended conformations supporting function |
title_full | Properdin oligomers adopt rigid extended conformations supporting function |
title_fullStr | Properdin oligomers adopt rigid extended conformations supporting function |
title_full_unstemmed | Properdin oligomers adopt rigid extended conformations supporting function |
title_short | Properdin oligomers adopt rigid extended conformations supporting function |
title_sort | properdin oligomers adopt rigid extended conformations supporting function |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857727/ https://www.ncbi.nlm.nih.gov/pubmed/33480354 http://dx.doi.org/10.7554/eLife.63356 |
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