Novel biochemical methods for facilitating GPCR tertiary and quaternary structure determination by cryo-EM.
EMSL Project ID
51491
Abstract
GPCRs are the largest family of membrane proteins in the human genome, and a major target of pharmaceutical drugs. However, relatively few GPCR structures are known. Moreover, many GPCRs are known to self-associate, yet few studies have reliably defined the structure of these dimers/multimers. To address these issues, we are developing novel methods to facilitate GPCR structural analysis by single-particle electron microscopy (cryo-EM) methods.
We will use these approaches to define the multimeric structure of two GPCRs; the “marijuana” receptor CB1, and the visual GPCR rhodopsin. We will also employ a novel bio-tag we have created for GPCR structural studies, using it to determine the first structure of a cone opsin, the photoreceptors responsible for color vision. This relatively small (~50 kDa) tag specifically binds GPCRs with high affinity and contains up to 52 metal ions that greatly increase contrast and facilitate cryo-EM analysis.
Project Details
Start Date
2020-06-15
End Date
2021-03-17
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members