Identification and analysis of dominant negative mutants of RIP1 DD that disrupt RIPoptosome core formation

Molecular Biology Reports
Hyun Ji Ha, Hyun Ho Park

Abstract

The RIPoptosome, composed of RIP1 and caspase-8, plays an important role in the regulation of apoptosis and necroptosis; however, the mechanism of complex formation by oligomerization and how the caspase-activating process and necroptosis are mediated by the formation of the RIPoptosome is not well-understood. This study revealed that the assembly mechanism of the RIPoptosome core is dependent on salt concentration and not on pH and time. In addition, we demonstrated that three RIP1 mutations, E626K, M637K, and S657K, have dominant negative effects. These dominant negative mutations in RIP1 may have potential applications in therapeutic intervention.

References

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Methods Mentioned

BETA
size-exclusion chromatography
gel filtration
pull-down
electron microscopy
size-exclusion column chromatography
pulldown

Software Mentioned

MODEL
Clustal Omega
PyMOL
PROCHECK
SWISS

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