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, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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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.
PY - 2021
Y1 - 2021
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.
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 -
ID: 257702103