Congratulations to SMB’s Steve Perkins for his recent publications from his group.
12 December 2019
Our congratulations to SMB’s Steve Perkins for his recent publications from his group.
One is in Biophysical Journal (part of Cell Press). This work was based on determinations of the solution conformations of the key monoclonal antibodies human IgG1 and IgG4. This was achieved by a joint X-ray and neutron solution scattering approach based on several instruments at four big facilities (Diamond, ISIS, ILL, ESRF), plus our analytical ultracentrifuges at UCL. We then fitted the data through a combination of molecular dynamics and Monte Carlo simulations to yield atomistic solution structures. The outcomes were very revealing in terms of receptor binding (see image).
Figure legend: Receptor binding to the best-fit IgG1 models. The antibody Fc structure is shown as a grey surface. The best-fit Fab orientations for IgG1 are shown in blue and yellow from all the possible Fab structures shown in pale grey. These Fab conformations permitted C1q and FcγRI receptor binding. Thus IgG1 is shown bound to a docked C1q head (green envelope), and to the FcγRI receptor (purple envelope).
We are now studying how their antibody conformations change when these antibodies are deglycosylated, with equally fascinating new insights. Another similar study of human myeloma IgG2 was published in J. Biol. Chem. earlier this year, showing that this has a different solution structure altogether from IgG1 and IgG4. Large industrial companies such as Fujifilm in Billingham and UCB in Slough have shown much interest in this solution structural approach, given that the market for these therapeutic monoclonal antibodies is around $70 billion per year.
The Perkins lab had participated in a multi-laboratory comparison of analytical ultracentrifuges in 2015. That paper received this accolade “Your article is among the top 10% most cited PLOS ONE papers published in 2015”, showing that this technology continues to be used widely in the Bioscience community. See https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0126420