Simulation of Neurotrophin Receptor Transmembrane Helix Interactions Reveals Active States and Distinct Signaling Mechanisms.

ABSTRACT: Neurotrophin (NT) receptor signaling regulates neuronal survival, axonal and dendritic network maintenance, differentiation, and synaptic plasticity. Signaling is initiated by binding of NT to the extracellular domain of NT receptor dimers, leading to activation of the receptor and signal propagation intracellularly. How this activating signal is mediated by the single-pass transmembrane (TM) helical domain of the receptor and what the relation between domain sequence and signaling mechanism is remain unclear. The structure and dynamics of the TM domain of the receptor dimers in the active and inactive states for intracellular signaling are still elusive, with NMR structures capturing only a single state. Here, we carried out unbiased and enhanced sampling molecular dynamics simulations of

SUBMITTER: Athanasiou C 

PROVIDER: S-EPMC12117394 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature