GPCR crystallization using lipidic cubic phase technique

Xin Yin, Henghao Xu, Michael Hanson, Wei Liu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

G protein-coupled receptors (GPCRs), a family of seven-transmembrane receptors, are among the most important drug targets with over half of all marketed drugs targeting the family. However, only a handful of easily druggable GPCRs are successfully targeted by pharmaceuticals. Efforts to shift this intensive focus to other, more recalcitrant GPCR targets will increasingly draw on new information such as structural details, which have until recently proven tremendously challenging to gather for this class of protein receptors due to the difficulties in obtaining diffraction-quality crystals. Recently, the development and application of lipidic cubic phase (LCP) technology has reduced one major hurdle for crystallization of GPCRs, with 22 unique receptors being structurally characterized from LCP grown crystals over the span of seven years. This review focuses on the technological improvements for LCP that have led to its successful utilization on the GPCR family, including the most recent combination of LCP with the X-ray free-electron laser that dramatically reduces requirements on crystal size, and holds significant promise for shortening timelines for structure determination and for accessing previously unattainable structures such as those of signaling complexes.

Original languageEnglish (US)
Pages (from-to)971-979
Number of pages9
JournalCurrent Pharmaceutical Biotechnology
Volume15
Issue number10
StatePublished - 2014
Externally publishedYes

Fingerprint

G-Protein-Coupled Receptors
Crystallization
Drug Delivery Systems
Pharmaceutical Preparations
Lasers
X-Rays
Electrons
Technology
Proteins

Keywords

  • G protein-coupled receptor (GPCR)
  • Lipidic cubic phase (LCP)
  • Membrane proteins
  • Serial Femtosecond Crystallography (SFX)
  • Structure-based drug design
  • X-ray free-electron laser (XFEL)

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Biotechnology
  • Medicine(all)

Cite this

GPCR crystallization using lipidic cubic phase technique. / Yin, Xin; Xu, Henghao; Hanson, Michael; Liu, Wei.

In: Current Pharmaceutical Biotechnology, Vol. 15, No. 10, 2014, p. 971-979.

Research output: Contribution to journalArticle

Yin, Xin ; Xu, Henghao ; Hanson, Michael ; Liu, Wei. / GPCR crystallization using lipidic cubic phase technique. In: Current Pharmaceutical Biotechnology. 2014 ; Vol. 15, No. 10. pp. 971-979.
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