EMBL-EBI, HEAD OF MACROMOLECULES, STRUCTURE, CHEMISTRY AND BIOIMAGING

Sameer Velankar leads the Protein Data Bank in Europe (PDBe)team at the EMBL-European Bioinformatics Institute. The team develops essential macromolecular structure resources and tools for biologists and other life scientists.
As a founding partner of the Worldwide Protein Data Bank organisation, we work on the Protein Data Bank (PDB). We also manage the community-led PDBe – Knowledge Base resource and the AlphaFold Protein Structure Database, a collaboration with DeepMind.
Our focus is on establishing a high-quality, up-to-date, andcomprehensive infrastructure by integrating 3D-structure data with biomedicaldata resources to provide enriched annotations.

PDBe team also continues to work on the development of anumber of innovative data analysis tools for 3D macromolecular structures tosupport its users.

The central role of FcRn in regulating immunoglobulin G (IgG) persistence and transport provides opportunities for targeting this receptor in multiple different diagnostic and therapeutic situations. The engineering of IgGs with higher affinity for FcRn can be used to produce antibodies with longer in vivo half-lives, but only if the low affinity of the IgG-FcRninteraction at near neutral pH is retained. Conversely, an engineered IgG or Fc fragmentwith increased affinity for FcRn at both acidic and near neutral pH acts as a potent inhibitor of FcRn. Consequently, such an antibody (‘Abdeg’, for antibody that enhancesIgG degradation) can lower the levels of endogenous IgG and has led to the FcRn antagonist, efgartigimod, that has been developed by argenx and recently approved for the treatment of myasthenia gravis. Our recent work has also resulted in the generation of engineered Fc-fusions that selectively clear antigen-specific antibodies (‘Seldegs’, for selective degradation). Developments related to the modulation of the dynamic behavior of IgG in the bodywill be presented.