Structural basis of synaptic receptor trafficking by PICK1
EMSL Project ID
51293
Abstract
Our goal is to determine the structural-functional mechanism by which the BAR domain protein PICK1 controls the trafficking of synaptic receptors, including AMPA and the dopamine transporter. Synaptic receptor trafficking affects synaptic strength, impacting vital physiological functions such as learning and memory. PICK1 contains an N-terminal PDZ domain, a classical banana-shaped BAR domain, and an acidic C-terminal tail (ACT). Recent findings show that PICK1 is regulated by interaction with another BAR domain protein, ICA69. We have developed anti-PICK1 nanobodies (Nb) and generated a rigid MBP-PICK1 fusion protein to aid the structural determination by increasing solubility and monodispersity, two conditions that so far hindered the investigation of this important protein. Our goal is to determine the structures of MBP-PICK1/Nb (202 kDa) and MBP-PICK1/ICA69 (288 kDa) complexes to help understand its function. This study will additionally illuminate the mechanisms by which BAR domain proteins associate with one another to control membrane curvature.
Project Details
Start Date
2020-03-15
End Date
2021-03-17
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members