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Nanobodies provide insight into the molecular mechanisms of the complement cascade and offer new therapeutic strategies

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The complement system is part of the innate immune response, where it provides imme-diate protection from infectious agents and plays a fundamental role in homeostasis. Complement dysregulation occurs in several diseases, where the tightly regulated proteolytic cascade turns of-fensive. Prominent examples are atypical hemolytic uremic syndrome, paroxysmal nocturnal he-moglobinuria and Alzheimer’s disease. Therapeutic intervention targeting complement activation may allow treatment of such debilitating diseases. In this review, we describe a panel of complement targeting nanobodies that allow modulation at different steps of the proteolytic cascade, from the activation of the C1 complex in the classical pathway to formation of the C5 convertase in the terminal pathway. Thorough structural and functional characterization has provided a deep mecha-nistic understanding of the mode of inhibition for each of the nanobodies. These complement specific nanobodies are novel powerful probes for basic research and offer new opportunities for in vivo complement modulation.

Original languageEnglish
Article number298
Number of pages24
Publication statusPublished - Feb 2021

    Research areas

  • Complement system, Convertase, Inhibitor, Molecular mechanism, Proteolytic cascade, Structural biology

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