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Properdin oligomers adopt rigid extended conformations supporting function

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Properdin oligomers adopt rigid extended conformations supporting function. / Pedersen, Dennis V.; Pedersen, Martin Nors; Mazarakis, Sofia M.M.; Wang, Yong; Lindorff-Larsen, Kresten; Arleth, Lise; Andersen, Gregers R.

In: eLife, Vol. 10, e63356, 01.2021.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Pedersen DV, Pedersen MN, Mazarakis SMM, Wang Y, Lindorff-Larsen K, Arleth L et al. Properdin oligomers adopt rigid extended conformations supporting function. eLife. 2021 Jan;10. e63356. https://doi.org/10.7554/eLife.63356

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Pedersen, Dennis V. ; Pedersen, Martin Nors ; Mazarakis, Sofia M.M. ; Wang, Yong ; Lindorff-Larsen, Kresten ; Arleth, Lise ; Andersen, Gregers R. / Properdin oligomers adopt rigid extended conformations supporting function. In: eLife. 2021 ; Vol. 10.

Bibtex

@article{078f1f6b597c40af9f4e4e50b7cc0c8e,
title = "Properdin oligomers adopt rigid extended conformations supporting function",
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 {\AA}. 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.",
author = "Pedersen, {Dennis V.} and Pedersen, {Martin Nors} and Mazarakis, {Sofia M.M.} and Yong Wang and Kresten Lindorff-Larsen and Lise Arleth and Andersen, {Gregers R.}",
note = "Publisher Copyright: {\textcopyright} 2021, eLife Sciences Publications Ltd. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = jan,
doi = "10.7554/eLife.63356",
language = "English",
volume = "10",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd.",

}

RIS

TY - JOUR

T1 - Properdin oligomers adopt rigid extended conformations supporting function

AU - Pedersen, Dennis V.

AU - Pedersen, Martin Nors

AU - Mazarakis, Sofia M.M.

AU - Wang, Yong

AU - Lindorff-Larsen, Kresten

AU - Arleth, Lise

AU - Andersen, Gregers R.

N1 - Publisher Copyright: © 2021, eLife Sciences Publications Ltd. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/1

Y1 - 2021/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85100078188&partnerID=8YFLogxK

U2 - 10.7554/eLife.63356

DO - 10.7554/eLife.63356

M3 - Journal article

C2 - 33480354

AN - SCOPUS:85100078188

VL - 10

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e63356

ER -