The control protein Factor H is a crucial regulator of the innate immune complement system, where it is active on host cell membranes and in the fluid phase. Mutations impairing the binding capacity of Factor H lead to severe autoimmune diseases. Here, we studied the solution structure of full-length Factor H, in its free state and bound to the C3b complement protein. To do so, we used two powerful techniques, hydroxyl radical protein footprinting and chemical cross-linking coupled with mass spectrometry, to probe the structural rearrangements and to identify protein interfaces. The footprint of C3b on the Factor H surface matches existing crystal structures of C3b complexed with the N- and C-terminal fragments of Factor H. In addition, we revealed the position of the central portion of Factor H in the protein complex. Moreover, cross-linking studies confirmed the involvement of the C-terminus in the dimerization of Factor H.
- Factor H
- C3b protein
- Complement system
- hydroxyl radical protein footprinting
- mass spectrometry
- ©2016 The Author(s)
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