A5049782656- Cell death mechanisms and regulation
- Nuclear Structure and Function
- Phagocytosis and Immune Regulation
- PARP inhibition in cancer therapy
- SARS-CoV-2 and COVID-19 Research
Walter and Eliza Hall Institute of Medical Research
2020-2021
Phosphorylation of the MLKL pseudokinase by RIPK3 kinase leads to oligomerization, translocation to, and permeabilization of, plasma membrane induce necroptotic cell death. The precise choreography activation remains incompletely understood. Here, we report Monobodies, synthetic binding proteins, that bind domain within human cells their crystal structures in complex with domain. While Monobody-32 constitutively binds hinge region, Monobody-27 via an epitope overlaps site is only exposed...
The necroptosis cell death pathway has been implicated in host defense and the pathology of inflammatory diseases. While phosphorylation necroptotic effector pseudokinase Mixed Lineage Kinase Domain-Like (MLKL) by upstream protein kinase RIPK3 is a hallmark activation, precise checkpoints signaling are still unclear. Here we have developed monobodies, synthetic binding proteins, that bind N-terminal four-helix bundle (4HB) “killer” domain neighboring first brace helix human MLKL with...