Death Receptor 5 Activation Is Energetically Coupled to Opening of the Transmembrane Domain Dimer.

ABSTRACT: The precise mechanism by which binding of tumor necrosis factor ligands to the extracellular domain of their corresponding receptors transmits signals across the plasma membrane has remained elusive. Recent studies have proposed that activation of several tumor necrosis factor receptors, including Death Receptor 5, involves a scissorlike opening of the disulfide-linked transmembrane (TM) dimer. Using time-resolved fluorescence resonance energy transfer, we provide, to our knowledge, the first direct biophysical evidence that Death Receptor 5 TM-dimers open in response to ligand binding. Then, to probe the importance of the closed-to-open TM domain transition in the overall energetics of receptor activation, we designed point-mutants (alanine to phenylalanine) in the predicted, tightly pack

SUBMITTER: Vunnam N 

PROVIDER: S-EPMC5529174 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature