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Updated: Dec 13, 2025

Crystallization of Membrane Proteins in Lipidic Mesophases

Crystallization of Membrane Proteins in Lipidic Mesophases

Published on: March 28, 2011

Structure Determination from Lipidic Cubic Phase Embedded Microcrystals by MicroED.

Lan Zhu¹, Guanhong Bu², Liang Jing¹

¹Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, 727 East Tyler Street, Tempe, AZ 85287, USA; School of Molecular Sciences, Arizona State University, 551 East University Drive, Tempe, AZ 85287, USA.

Structure (London, England : 1993)

|August 1, 2020

Summary

This summary is machine-generated.

The lipidic cubic phase (LCP) technique aids in growing difficult crystals. Combining LCP with microcrystal electron diffraction (MicroED) enables high-resolution structure determination from these small crystals, especially for challenging membrane proteins.

Keywords:

GPCR Proteinase K additive phase conversion cholesterol cryo-electron microscopy (cryo-EM)lipase hydrolysis lipidic cubic phase (LCP)membrane protein microcrystal electron diffraction (MicroED)microcrystallography

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Last Updated: Dec 13, 2025

Crystallization of Membrane Proteins in Lipidic Mesophases

Crystallization of Membrane Proteins in Lipidic Mesophases

Published on: March 28, 2011

From Constructs to Crystals – Towards Structure Determination of β-barrel Outer Membrane Proteins

From Constructs to Crystals – Towards Structure Determination of β-barrel Outer Membrane Proteins

Published on: July 4, 2016

Crystallizing Membrane Proteins for Structure Determination using Lipidic Mesophases

Crystallizing Membrane Proteins for Structure Determination using Lipidic Mesophases

Published on: November 21, 2010

Area of Science:

Structural Biology
Biophysics
Crystallography

Background:

The lipidic cubic phase (LCP) technique is crucial for growing high-quality crystals of proteins that are difficult to crystallize using conventional methods.
Optimizing crystal size for structure determination can be resource-intensive and time-consuming.
Developing advanced structure determination techniques for small crystals is vital for diffraction technology.

Purpose of the Study:

To investigate the combined application of modified lipidic cubic phase (LCP) and microcrystal electron diffraction (MicroED) protocols.
To demonstrate the feasibility of MicroED for analyzing microcrystalline samples grown in LCP.
To overcome challenges in determining structures from small or difficult-to-crystallize samples, particularly membrane proteins.

Main Methods:

Crystals were grown using the lipidic cubic phase (LCP) technique.
LCP-embedded crystals were converted using 2-methyl-2,4-pentanediol or lipase.
Microcrystal electron diffraction (MicroED) data were collected using cryo-transmission electron microscopy.
Protocols were modified for enhanced LCP and MicroED analysis.

Main Results:

Successfully applied modified LCP and MicroED protocols to analyze various crystals.
Analyzed Proteinase K crystals (solution-grown), cholesterol crystals, and human adenosine A2A receptor crystals (LCP-grown).
Demonstrated high-resolution structure determination from microcrystalline samples embedded in LCP.

Conclusions:

The integration of modified LCP and MicroED offers a powerful strategy for structure determination.
This approach is particularly promising for analyzing challenging membrane protein targets crystallized in LCP.
The study establishes a foundation for utilizing MicroED with LCP-grown microcrystals.