The complement system is an evolutionary ancient immune defense mechanism, present in vertebrates and invertebrates. It forms a first line of defense in plasma and fluids surrounding tissues and enables the host to recognize and clear invading pathogens (bacteria and viruses) and altered host cells while protecting healthy host cells and tissues. In humans this system is formed by more than 30 large modular plasma proteins and cell surface receptors.
We study the complement system using a variety of biophysical techniques including X-ray Crystallography and Cryo-Electron Microscopy.
Membrane proteins comprise 20-30% of proteins in the genome, but are targeted by over 50% of modern pharmaceuticals.
We study a number of membrane proteins using a variety of biophysical techniques including X-ray Crystallography and Cryo-Electron Microscopy.
We have worked on a variety of crystallographic methods for determining molecular structures or proteins with crystallography. These methods include:
Multi-dataset crystallographic methods, utilising multiple crystallographic datasets during structure solution
Ensemble Refinement, a method for combining Molecular Dynamics simulations with experimental diffraction data
Conditional Optimisation, a novel method for refinement, automated model building and ab initio phasing
X-ray structures of monomeric properdin and its complex with the CTC-domain of C3b.
Cryo-EM structures of human STEAP4 bound to NADP, FAD, heme, in presence and absence of Fe(III)-NTA.
X-ray structures of C3b and C3b in complex with various defence proteins (MCP, CR1 & DAF).
X-ray structures of R-spondin 1 and its complex with LGR5.
X-ray structures of factor D and factor D in complex with C3b and factor B (C3bBD).
X-ray structure of cobra venom factor (CVF) in complex with human factor B.
X-ray structures of the translocator domain of Neisseria meningitidis NalP.
Density map of C1 with bound C4b on a hexemeric IgM platform.
Density maps at 10-Å resolution for the whole C1-IgG16 complex and 7-Å resolution for the hexameric gC1q-Fc platform
Substrate C3 is superposed on the S. aureus SCIN inhibited C3 convertase C3bBb dimer.
Morph showing the changes between the structures of C3 and C3b.
Coloured by domain
Disease related mutations mapped onto the structure of C3b-FH(1-4).