Flexibility in Mannan-Binding Lectin-Associated Serine Proteases-1 and-2 Provides Insight on Lectin Pathway Activation. Nan, R., Furze, C. M., Wright, D. W., Gor, J., Wallis, R., & Perkins, S. J. Structure, 25(2):364–375, February, 2017. Place: Cambridge Publisher: Cell Press WOS:000396702700017
doi  abstract   bibtex   
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 Ca2+-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 degrees 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.
@article{nan_flexibility_2017,
	title = {Flexibility in {Mannan}-{Binding} {Lectin}-{Associated} {Serine} {Proteases}-1 and-2 {Provides} {Insight} on {Lectin} {Pathway} {Activation}},
	volume = {25},
	issn = {0969-2126},
	doi = {10.1016/j.str.2016.12.014},
	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 Ca2+-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 degrees 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.},
	language = {English},
	number = {2},
	journal = {Structure},
	author = {Nan, Ruodan and Furze, Christopher M. and Wright, David W. and Gor, Jayesh and Wallis, Russell and Perkins, Stephen J.},
	month = feb,
	year = {2017},
	note = {Place: Cambridge
Publisher: Cell Press
WOS:000396702700017},
	keywords = {classical pathway, complement activation, complexes, crystal-structure, masp-1, naturally-occurring mutations, protein, recognition, structural basis, x-ray-structure},
	pages = {364--375}
}
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