Molecular mechanism of sialic-acid mediated self-recognition by complement factor H

• Applicant: Dr. Bärbel Blaum
• Subject Area: Immunology ; Biochemistry ; Structural Biology
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 261757462

The complement system is an important part of innate immunity, enabling infection defense without prior exposure and generation of specific anti bodies. Healthy host cells require active protection from the complement alternative pathway, and a number of regulatory proteins are charged with this task. One mechanism by which the complement regulator factor H (CFH) identifies and shields host cells from auto immune attack is at the centre of this proposal. Sialic acid host markers for factor H have been and further will be structurally characterized in the course of the project, and the CFH-sialic acid recognition process will be elucidated with the help of nuclear magnetic resonance spectroscopy and protein crystallography on the molecular level. The thus obtained complex structures will be verified by structure-guided mutagenesis and physiological assays and will, in the long run, serve as a platform to modulate CFH binding to host glycans for therapeutic purposes.

• DFG Programme: Research Grants