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Detergent-free extraction of membrane proteins and lipids from native cells


EMSL Project ID
60481

Abstract

Membrane proteins account for >30% of most genomes, yet only make up <4% of reported high-resolution structures in the protein data bank. Current approaches for isolating membrane proteins from native cells are tedious, labor intensive, and require "mild" detergents that alter the native protein structure and lipid environment. The objective of this project is to engineer a library of synthetic “scaffolds proteins” that bypass detergent solubilization procedures to directly extract membrane protein-lipid complexes into affinity purifiable nanodiscs. To achieve this objective, we will fuse anti-microbial peptides (AMPs) to commercially available membrane scaffold proteins (MSP). AMPs contain the inherent ability to naturally disrupt and “dig” out cell membrane constituents. By conferring these detergent-like qualities of AMPs to the MSP scaffold, we will generate a reagent capable of directly extract membrane proteins and surrounding lipids into nanodiscs for structure-function analysis. We will use the MSP-AMP library to capture membrane proteins and surrounding lipids from two model organisms important for biofuel production: the algae Ostreococcus tauri and the yeast Yarrowia lipolytica. Upon successful extraction and demonstration of proof-of-principle, we will make the library available to the EMSL user community.

Project Details

Start Date
2022-10-01
End Date
N/A
Status
Active

Team

Principal Investigator

John Melchior
Institution
Pacific Northwest National Laboratory

Team Members

Mischelle Schutz
Institution
Pacific Northwest National Laboratory

Madelyn Berger
Institution
Pacific Northwest National Laboratory

Samantha Powell
Institution
Pacific Northwest National Laboratory

Erin Bredeweg
Institution
Environmental Molecular Sciences Laboratory

Jennifer Kyle
Institution
Pacific Northwest National Laboratory

James Evans
Institution
Environmental Molecular Sciences Laboratory