A review of factors affecting the success of membrane protein crystallization using bicelles

Abstract

Several reports have been published detailing various platforms for obtaining crystals of membrane proteins to determine their structure including those that use disk shaped bilayers called bicelles. While these crystals have been readily grown and used for x-ray diffraction, the general understanding as to why bicelles are adequate for such a procedure or how to rationally choose conditions remains unknown. This review intends to discuss issues of protein stabilization and precipitation in the presence of lipids that may influence crystal formation.

Magnetically Oriented Bicelles with Monoalkylphosphocholines: Versatile Membrane Mimetics for Nuclear Magnetic Resonance Applications

“…The planar region made of long-chain phospholipids constitutes a favorable environment to study molecular interactions as well as the structure of membrane peptides and proteins with different biophysical techniques such as nuclear magnetic resonance (NMR), circular dichroism and fluorescence [3][4][5][6][7][8][9] . Bicelles can also be used to obtain protein crystals for X-ray crystallography 10,11 and have potential pharmaceutical applications [12][13][14][15][16] . In particular, bicelles have proven to be an ideal mimetic for solid-state NMR as they provide an ideal support for integral membrane proteins in a near native environment.…”

“…Bilayered micelles, or so-called bicelles, were introduced in the 1990s and quickly gained popularity because of their similarities with biological membranes. , They are composed of long-chain phospholipids organized in a bilayer stabilized by short-chain lipids or detergents in the high-curvature region of discs or perforated vesicles. The planar region made of long-chain phospholipids constitutes a favorable environment for studying molecular interactions as well as the structure of membrane peptides and proteins with different biophysical techniques such as nuclear magnetic resonance (NMR), circular dichroism, and fluorescence. − Bicelles can also be used to obtain protein crystals for X-ray crystallography , and have potential pharmaceutical applications. − In particular, bicelles have proven to be an ideal mimetic for solid-state NMR because they provide an ideal support for integral membrane proteins in a near native environment. Moreover, they are not limited by the solubility, the size of the macromolecules or complex, or the requirement of crystals .…”