The molecular recognition and function of the TGFβ1 – neuropilin interaction: a computational, biophysical and biological study.

David Selwood (primary)
Wolfson Institute for Biomedical Research
UCL
Snezana Djordjevic (secondary)
Institute for Structural and Molecular Biology
UCL/Birkbeck

Abstract

Immune targeting agents are transforming the treatment of cancer. We have identified the TGFβ1 – NRP1interaction as an important signaling axis in controlling the immune response to tumours. This project works out the details of the molecular interactions for TGFβ1 – NRP1using computational, biophysical and cell biology methods. The results will provide fundamental knowledge important in the development of new therapies for cancer.


References

1 Nissen JC, Selwood DL, Tsirka SE. Tuftsin signals through its receptor
neuropilin-1 via the transforming growth factor beta pathway. J Neurochem. 2013
Nov;127(3):394-402. doi: 10.1111/jnc.12404. PMID: 24033337.
2 Miyauchi JT, Chen D, Choi M, Nissen JC, Shroyer KR, Djordevic S, Zachary IC,
Selwood D, Tsirka SE. Ablation of NRP11 from glioma-associated microglia
and macrophages slows tumor progression. Oncotarget. 2016 Mar 1;7(9):9801-14.
doi: 10.18632/oncotarget.6877. PMID: 26755653.
3 Powell J, …Djordjevic S, Tsirka SE, Zachary IC, Selwood DL. Small Molecule Neuropilin-1 Antagonists Combine Antiangiogenic and Antitumor Activity with Immune Modulation through Reduction of Transforming Growth Factor Beta (TGFβ1) Production in Regulatory T-Cells. J Med Chem. 2018 May 10;61(9):4135-4154. doi:10.1021/acs.jmedchem.8b00210. PMID: 29648813.
4 Mota F, Fotinou C, Rana RR, Chan AWE, Yelland T, Arooz MT, O’Leary AP, Hutton
J, Frankel P, Zachary I, Selwood D, Djordjevic S. Architecture and hydration of
the arginine-binding site of neuropilin-1. FEBS J. 2018 Apr;285(7):1290-1304.
doi: 10.1111/febs.14405. PMID: 29430837.


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
Cell Biology
Techniques & Approaches
BiochemistryBioinformaticsBiophysicsMathematics / StatisticsMolecular BiologySimulation / Modelling