Atomic force microscopy study of innate immune response complexes

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Project objective

The complement system is important in the first-line defense against infections and for the generation of specific immune reactions. The mannan-binding lectin (MBL) and the MBL-associated serine proteases (MASPs) provide a recently discovered pathway to the activation of complement. Low levels of MBL are linked to an increased susceptibility to microbial infections and autoimmune diseases. The understanding of the MBL pathway and the mechanism of activation remain largely speculative. The goal of this project is to study the structure of the MBL/MASP complex and the structural changes associated with the activation of the MASPs with sophisticated atomic force microscopy (AFM) techniques. The first aim of this project is to localize, for the first time, the MASPs in the complex. For this, a modified AFM-tip using mannose-fictionalized carbon nanotubes will yield chemical contrast which allows to distinguish clearly between the sugar recognizing domains of the MBL and the MASPs in the complex. The subsequent aim is to directly visualize the proposed conformational change of the complex on activation. I will study the mechanics of the activation of the complex using the AFM's ability to study biomolecules at work in native environments.

Original text from CORDIS.

Participants

• LEIDEN UNIVERSITY · LEIDENCoordinatorNetherlands

Links

• View on CORDIS