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|Title:||Flexibility in Mannan-Binding Lectin-Associated Serine Proteases-1 and -2 Provides Insight on Lectin Pathway Activation.|
Furze, Christopher M.
Wright, D. W.
Perkins, S. J.
|Publisher:||Elsevier (Cell Press)|
|Citation:||Structure, 2017 25, 1–12|
|Abstract:||The lectin pathway of complement is activated by complexes comprising a recognition component (mannose-binding lectin, serum ficolins, collectin-LK or collectin-K1) and a serine protease (MASP-1 or MASP-2). MASP-1 activates MASP-2, and MASP-2 cleaves C4 and C4b-bound C2. To clarify activation, new crystal structures of Ca(2+)-bound MASP dimers were determined, together with their solution structures from X-ray scattering, analytical ultracentrifugation, and atomistic modeling. Solution structures of the CUB1-EGF-CUB2 dimer of each MASP indicate that the two CUB2 domains were tilted by as much as 90° compared with the crystal structures, indicating considerable flexibility at the EGF-CUB2 junction. Solution structures of the full-length MASP dimers in their zymogen and activated forms revealed similar structures that were much more bent than anticipated from crystal structures. We conclude that MASP-1 and MASP-2 are flexible at multiple sites and that this flexibility may permit both intra- and inter-complex activation.|
|Rights:||This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).|
|Description:||Supplemental Information includes Supplemental Experimental Procedures, two figures, one table, and six pdb files and can be found with this article online at http://dx.doi.org/10.1016/j.str.2016.12.014.|
|Appears in Collections:||Published Articles, Dept. of Infection, Immunity and Inflammation|
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