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Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/98724
Título

Structural basis for the stabilization of the complement alternative pathway C3 convertase by properdin

AutorAlcorlo, Martín ; Tortajada, Agustín ; Rodríguez de Córdoba, Santiago ; Llorca, Óscar
Palabras claveProperdin
C3b
AP C3 convertase
Complement
Electron microscopy
EM
Fecha de publicaciónjul-2013
EditorNational Academy of Sciences (U.S.)
CitaciónPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 110: 13504- 13509 (2013)
ResumenComplement 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 (thioestercontaining 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.
Descripción33 p.-4 fig.-2 fig. supl.
Versión del editorhttp://dx.doi.org/10.1073/pnas.1309618110
URIhttp://hdl.handle.net/10261/98724
DOI10.1073/pnas.1309618110
E-ISSN1091-6490
Identificadoresdoi: 10.1073/pnas.1309618110
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