Mechanism of complement inhibition by a mosquito protein revealed through cryo-EM.
Commun Biol
; 7(1): 649, 2024 May 27.
Article
em En
| MEDLINE
| ID: mdl-38802531
ABSTRACT
Salivary complement inhibitors occur in many of the blood feeding arthropod species responsible for transmission of pathogens. During feeding, these inhibitors prevent the production of proinflammatory anaphylatoxins, which may interfere with feeding, and limit formation of the membrane attack complex which could damage arthropod gut tissues. Salivary inhibitors are, in many cases, novel proteins which may be pharmaceutically useful or display unusual mechanisms that could be exploited pharmaceutically. Albicin is a potent inhibitor of the alternative pathway of complement from the saliva of the malaria transmitting mosquito, Anopheles albimanus. Here we describe the cryo-EM structure of albicin bound to C3bBb, the alternative C3 convertase, a proteolytic complex that is responsible for cleavage of C3 and amplification of the complement response. Albicin is shown to induce dimerization of C3bBb, in a manner similar to the bacterial inhibitor SCIN, to form an inactive complex unable to bind the substrate C3. Size exclusion chromatography and structures determined after 30 minutes of incubation of C3b, factor B (FB), factor D (FD) and albicin indicate that FBb dissociates from the inhibited dimeric complex leaving a C3b-albicin dimeric complex which apparently decays more slowly.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas e Peptídeos Salivares
/
Complemento C3b
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Proteínas de Insetos
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Anopheles
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Commun Biol
/
Commun. biolog
/
Communications biology
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos