Fig. 7: Schematic diagram of proposed mechanism underlying conformational signaling of ASIC1a in acidotoxicity. | Nature Communications

Fig. 7: Schematic diagram of proposed mechanism underlying conformational signaling of ASIC1a in acidotoxicity.

From: Disruption of auto-inhibition underlies conformational signaling of ASIC1a to induce neuronal necroptosis

Fig. 7

Under normal conditions, the CP-1 death motif of ASIC1a-CT is masked by interaction with ASIC1a-NT (left). Acidosis activates ASIC1a and causes conformational transition that disrupts the preformed N- to C-terminal interaction within ASIC1a to unmask the CT death motif. This transition is facilitated and stabilized by NSF binding to ASIC1a-NT. The freed ASIC1a-CT recruits RIPK1 and activates it by phosphorylation, resulting in neuronal necroptosis (middle). Peptide NT1–20 binds to ASIC1a-CT to prevent recruitment and thereby activation of RIPK1 to achieve neuroprotection (right). NT1–20 may also bind to NSF, decreasing its availability for ASIC1a-NT, similar to NSF shRNA knockdown or inhibition by NEM.

Back to article page