5ckq
From Proteopedia
CUB1-EGF-CUB2 domains of rat MASP-1
Structural highlights
Function[MASP1_RAT] Functions in the lectin pathway of complement, which performs a key role in innate immunity by recognizing pathogens through patterns of sugar moieties and neutralizing them. The lectin pathway is triggered upon binding of mannan-binding lectin (MBL) and ficolins to sugar moieties which leads to activation of the associated proteases MASP1 and MASP2. Functions as an endopeptidase and may activate MASP2 or C2 or directly activate C3 the key component of complement reaction. Isoform 2 may have an inhibitory effect on the activation of the lectin pathway of complement or may cleave IGFBP5 (By similarity). Publication Abstract from PubMedThe 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. Flexibility in Mannan-Binding Lectin-Associated Serine Proteases-1 and -2 Provides Insight on Lectin Pathway Activation.,Nan R, Furze CM, Wright DW, Gor J, Wallis R, Perkins SJ Structure. 2017 Jan 18. pii: S0969-2126(16)30404-X. doi:, 10.1016/j.str.2016.12.014. PMID:28111019[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Furze, C M | Gor, J | Nan, R | Perkins, S J | Wallis, R | Wright, D W | Complement | Cub1-egf-cub2 | Hydrolase | Lectin pathway | Serine protease
