Yang Liu, Tom D Bunney, Sakshi Khosa, Kévin Macé, Katharina Beckenbauer, Trevor Askwith, Sarah Maslen, Christopher Stubbs, Taiana M de Oliveira, Kasim Sader, Mark Skehel, Anne-Claude Gavin, Christopher Phillips, Matilda Katan
BACKGROUND: PLCγ enzymes are key nodes in cellular signal transduction and their mutated and rare variants have been recently implicated in development of a range of diseases with unmet need including cancer, complex immune disorders, inflammation and neurodegenerative diseases. However, molecular nature of activation and the impact and dysregulation mechanisms by mutations, remain unclear; both are critically dependent on comprehensive characterization of the intact PLCγ enzymes. METHODS: For structural studies we applied cryo-EM, cross-linking mass spectrometry and hydrogen-deuterium exchange mass spectrometry...
January 6, 2020: EBioMedicine