5CKM

The CUB1-EGF-CUB2 domains of rat MBL-associated serine protease-2 (MASP-2) bound to Ca2+

Summary for 5CKM

• Entry DOI: 10.2210/pdb5ckm/pdb
• Descriptor: Mannan-binding lectin serine peptidase 2, CALCIUM ION, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: masp, cub1-egf-cub2, complement activation, lectin pathway, hydrolase
• Biological source: Rattus norvegicus (Norway Rat)
• Total number of polymer chains: 1
• Total formula weight: 31740.29

Authors

Nan, R.,Furze, C.M.,Wright, D.W.,Gor, J.,Wallis, R.,Perkins, S.J. (deposition date: 2015-07-15, release date: 2017-01-18, Last modification date: 2024-10-16)

Primary citation

Nan, R.,Furze, C.M.,Wright, D.W.,Gor, J.,Wallis, R.,Perkins, S.J.
Flexibility in Mannan-Binding Lectin-Associated Serine Proteases-1 and -2 Provides Insight on Lectin Pathway Activation.
Structure, 25:364-375, 2017

PubMed 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-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.

PubMed: 28111019
DOI: 10.1016/j.str.2016.12.014

Experimental method

X-RAY DIFFRACTION (2.73 Å)