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Flexibility in Mannan-Binding Lectin-Associated Serine Proteases-1 and -2 Provides Insight on Lectin Pathway Activation.

<div class='caption-title'>Domain Organization of MASP and Its MASP-MBL Complex</div>
<div class='caption-title'>Crystal Structures of MASP-1 and MASP-2 3D Dimers and Their Ca2+-Binding Sites</div>
<div class='caption-title'>SAXS Guinier and P(r) Analyses</div>
Nan R, Furze CM, Wright DW, Gor J, Wallis R, Perkins SJ
OpenAccess logo Structure 25 364-375 (2017)
Related entries: 5cis, 5ckm, 5ckn

Cited: 8 times
EuropePMC logo PMID: 28111019

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° 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.

Articles - 5ckq mentioned but not cited (1)

  1. 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 25 364-375 (2017)


Reviews citing this publication (2)

  1. Complement in neurological disorders and emerging complement-targeted therapeutics. Dalakas MC, Alexopoulos H, Spaeth PJ. Nat Rev Neurol 16 601-617 (2020)
  2. Complement System in Alzheimer's Disease. Shah A, Kishore U, Shastri A. Int J Mol Sci 22 13647 (2021)

Articles citing this publication (5)

  1. Atomistic modelling of scattering data in the Collaborative Computational Project for Small Angle Scattering (CCP-SAS). Perkins SJ, Wright DW, Zhang H, Brookes EH, Chen J, Irving TC, Krueger S, Barlow DJ, Edler KJ, Scott DJ, Terrill NJ, King SM, Butler PD, Curtis JE. J Appl Crystallogr 49 1861-1875 (2016)
  2. Structure of the C1r-C1s interaction of the C1 complex of complement activation. Almitairi JOM, Venkatraman Girija U, Furze CM, Simpson-Gray X, Badakshi F, Marshall JE, Schwaeble WJ, Mitchell DA, Moody PCE, Wallis R. Proc Natl Acad Sci U S A 115 768-773 (2018)
  3. MASP-1 of the complement system enhances clot formation in a microvascular whole blood flow model. Jenny L, Dobó J, Gál P, Pál G, Lam WA, Schroeder V. PLoS One 13 e0191292 (2018)
  4. Non-linearity of the collagen triple helix in solution and implications for collagen function. Walker KT, Nan R, Wright DW, Gor J, Bishop AC, Makhatadze GI, Brodsky B, Perkins SJ. Biochem J 474 2203-2217 (2017)
  5. Lectin Pathway Enzyme MASP-2 and Downstream Complement Activation in COVID-19. Götz MP, Skjoedt MO, Bayarri-Olmos R, Hansen CB, Pérez-Alós L, Jarlhelt I, Benfield T, Rosbjerg A, Garred P. J Innate Immun 15 122-135 (2023)


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