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-Structure paper
タイトル | Structural basis for the stabilization of the complement alternative pathway C3 convertase by properdin. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 110, Issue 33, Page 13504-13509, Year 2013 |
掲載日 | 2013年8月13日 |
著者 | Martín Alcorlo / Agustín Tortajada / Santiago Rodríguez de Córdoba / Oscar Llorca / |
PubMed 要旨 | Complement is an essential component of innate immunity. Its activation results in the assembly of unstable protease complexes, denominated C3/C5 convertases, leading to inflammation and lysis. ...Complement is an essential component of innate immunity. Its activation results in the assembly of unstable protease complexes, denominated C3/C5 convertases, leading to inflammation and lysis. Regulatory proteins inactivate C3/C5 convertases on host surfaces to avoid collateral tissue damage. On pathogen surfaces, properdin stabilizes C3/C5 convertases to efficiently fight infection. How properdin performs this function is, however, unclear. Using electron microscopy we show that the N- and C-terminal ends of adjacent monomers in properdin oligomers conform a curly vertex that holds together the AP convertase, interacting with both the C345C and vWA domains of C3b and Bb, respectively. Properdin also promotes a large displacement of the TED (thioester-containing domain) and CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domains of C3b, which likely impairs C3-convertase inactivation by regulatory proteins. The combined effect of molecular cross-linking and structural reorganization increases stability of the C3 convertase and facilitates recruitment of fluid-phase C3 convertase to the cell surfaces. Our model explains how properdin mediates the assembly of stabilized C3/C5-convertase clusters, which helps to localize complement amplification to pathogen surfaces. |
リンク | Proc Natl Acad Sci U S A / PubMed:23901101 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 23.4 - 29.3 Å |
構造データ | EMDB-2402: EMDB-2403: |
由来 |
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