Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/39338
Title: Flexibility in Mannan-Binding Lectin-Associated Serine Proteases-1 and -2 Provides Insight on Lectin Pathway Activation.
Authors: Nan, R.
Furze, Christopher M.
Wright, D. W.
Gor, J.
Wallis, Russell
Perkins, S. J.
First Published: 18-Jan-2017
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.
DOI Link: 10.1016/j.str.2016.12.014
ISSN: 0969-2126
eISSN: 1878-4186
Links: http://www.sciencedirect.com/science/article/pii/S096921261630404X
http://hdl.handle.net/2381/39338
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
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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