EMD-42300

Single-particle
3.86 Å
EMD-42300 Deposition: 10/10/2023
Map released: 08/05/2024
Last modified: 12/06/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-42300

Structure of the C3bBb-albicin complex

EMD-42300

Single-particle
3.86 Å
EMD-42300 Deposition: 10/10/2023
Map released: 08/05/2024
Last modified: 12/06/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Anopheles albimanus
Sample: complex of C3bBb with the inhibitor albicin
Fitted models: 8uin (Avg. Q-score: 0.379)

Deposition Authors: Andersen JF , Lei H
Mechanism of complement inhibition by a mosquito protein revealed through cryo-EM.
Andersen JF , Lei H , Strayer EC, Pham V, Ribeiro JMC
(2024) Commun Biol , 7 , 649 - 649
PUBMED: 38802531
DOI: doi:10.1038/s42003-024-06351-x
ISSN: 2399-3642
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.