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Review
. 2011 Aug;21(4):559-66.
doi: 10.1016/j.sbi.2011.06.007. Epub 2011 Jul 19.

Lipidic cubic phase technologies for membrane protein structural studies

Affiliations
Review

Lipidic cubic phase technologies for membrane protein structural studies

Vadim Cherezov. Curr Opin Struct Biol. 2011 Aug.

Abstract

Lipidic cubic phase (LCP) is a membrane-mimetic matrix suitable for stabilization and crystallization of membrane proteins in lipidic environment. LCP technologies, however, have not been fully embraced by the membrane protein structural biology community, primarily because of the difficulties associated with handling viscous materials. Recent developments of pre-crystallization assays and improvements in crystal imaging, successes in obtaining high resolution structures of G protein-coupled receptors (GPCRs), and commercial availability of LCP tools and instruments are beginning to attract structural biologists to integrate LCP technologies in their research. This wider acceptance should translate to an increased number of otherwise difficult-to-crystallize membrane protein structures, shedding light on their functional mechanisms and on structural details of lipid-protein interactions.

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Figures

Figure 1
Figure 1
A gallery of protein and peptide structures obtained by LCP crystallization. For each unique protein the highest resolution and corresponding PDB ID are shown.
Figure 2
Figure 2
Growth of membrane protein structures obtained by LCP crystallization with time. (a) All structures deposited to PDB. (b) Unique structures (defined as those, in which the protein sequence differs by more than 10%).
Figure 3
Figure 3
LCP Toolchest: collection of tools and assays for preparation and handling of LCP, and for characterization and crystallization of membrane proteins in LCP. (a) Lipid syringe mixer for LCP preparation [46]; (b) manual LCP dispenser [47]; (c) in meso crystallization robot [21]; (d) Novel LCP forming lipids for host lipid screening [,–28]; (e) 96-well glass sandwich crystallization plate [22,33]; (f) Improved LCP crystal imaging; (g) LCP-FRAP assay [16]; (h) LCP-Tm assay [15]; (i) LCP-SONICC [37]; (j) LCP-SAXS [48].

References

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    1. Jaakola VP, Griffith MT, Hanson MA, Cherezov V, Chien EY, Lane JR, Ijzerman AP, Stevens RC. The 2. 6 Angstrom Crystal Structure of a Human A2A Adenosine Receptor Bound to an Antagonist. Science. 2008;322:1211–1217. - PMC - PubMed
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    1. Chien EY, Liu W, Zhao Q, Katritch V, Han GW, Hanson MA, Shi L, Newman AH, Javitch JA, Cherezov V, et al. Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science. 2010;330:1091–1095. Structure of the human dopamine D3 receptor obtained by LCP crystallization. - PMC - PubMed
    1. Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han GW, et al. Structure of the human histamine H1 receptor complex with doxepin. Nature. 2011 in press. Structure of the human histamine H1 receptor obtained by LCP crystallization. - PMC - PubMed

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