Celebrating I03's 1000th PDB entry
This week beamline I03 is celebrating a milestone; 1000 entries into the Protein Data Bank (PDB)!
Industrial Users Magnus Life Science, based at University College London, identified and structurally characterised a zinc ion binding site on human neuropilin-2.
Neuropilin-2 is a transmembrane receptor involved in lymphangiogenesis and neuronal development. In adults, neuropilin-2 and its homologous protein neuropilin-1 have been implicated in infection and physiological and disease‐related processes in adult organisms, such as various cancers, but until now molecular determinants of the ligand selectivity of neuropilins have been poorly understood.
The researchers from UCL and Magnus Life Science have shown that the neuropilin-2-specific zinc ion binding site is located near the interface between domains b1 and b2 in the ectopic region of the protein, remote from the neuropilin binding site for its physiological ligand, i.e. vascular endothelial growth factor. The X-ray crystal structure of the neuropilin-2 b1 domain in a complex with the C-terminal sub-domain of VEGF-A. Zn(2+) binding to neuropilin-2 was shown to destabilise the protein structure but the effect was counteracted by heparin, suggesting that modifications by glycans and zinc in the extracellular matrix may affect functional neuropilin-2 ligand binding and signalling activity. These findings will pave the way for further exploration of the effects of zinc homeostasis on neuropilin functions and ligand binding.
Magnus Life Science is a creative biomedical organisation that funds, builds and manages companies to translate innovative, curiosity driven science into therapeutics and devices that bring significant benefits to patients. Magnus has a unique ‘spin-in’ model. Through an industrial collaboration, the Company’s operational and R&D teams are located within UCL with renowned experts who are practising clinicians working closely with an experienced management team to take the academic, commercial and clinical lead on projects.
Read more on the PDB website here
Structural studies of neuropilin-2 reveal a zinc ion binding site remote from the vascular endothelial growth factor binding pocket. Tsai, Y.C., Fotinou, C., Rana, R., Yelland, T., Frankel, P., Zachary, I., Djordjevic, S. (2016) Febs J. 283: 1921-1934 DOI: 10.1111/febs.13711