Architecture and subunit composition of native mammalian AMPA receptors
EMSL Project ID
51007
Abstract
The objectives of this research are to elucidate the structures of native mammalian, AMPA-selective ionotropic glutamate receptors (iGluRs) by single particle cryo-EM in distinct conformational states stabilized by selected agonists, antagonists, allosteric modulators and/or ion channel pore blockers. Because these native receptors are isolated under mild conditions, we copurify AMPA receptor auxiliary subunits, allowing us to determine the structure and composition of native AMPA receptor-auxiliary protein complexes. We have developed novel monoclonal antibody fragments (Fab or scFv) to isolate the native receptors and to employ in 3D classification to enable identification of the heteromeric receptor complexes. Because nearly all structural studies to date have focused on homomeric, recombinant receptors, yet native receptors are nearly all heteromers, our work will provide new insight into native AMPA receptor architecture, subunit arrangement and mechanism.
Project Details
Start Date
2019-09-01
End Date
2021-03-17
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members