title: Successful Strategies to Determine High-Resolution Structures of GPCRs.
abstract: G protein-coupled receptors (GPCRs) constitute the largest class of drug targets in the human genome, which highlights the importance of understanding the molecular basis of their activation, downstream signaling, and regulation. Since 2007, great progress has been made in the field of GPCR structure determination and their signaling complexes at the molecular level. Here, we summarize the high-resolution structures of over 30 different GPCRs with their co-crystallized ligands, and outline the successful strategies involved, including construct design, expression systems, and lipidic cubic phase (LCP) composition, and the many key technical parameters of the crystallization methods. By comparing the success rates of different strategies used in the past, we wish to pave the road for more successful structure-function research for GPCRs in the future.
authors.affiliation: School of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287-1604, USA; Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Science, Wuhan University, Wuhan 430071, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xiang
authors.affiliation: School of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287-1604, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Chun
authors.affiliation: School of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287-1604, USA.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: School of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287-1604, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Jing
authors.affiliation: School of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287-1604, USA.
authors.forename: Zina
authors.initials: Z
authors.lastname: Al-Sahouri
authors.affiliation: School of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287-1604, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: School of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287-1604, USA. Electronic address: w.liu@asu.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D003460:Crystallization; D015894:Genome, Human; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000737:chemistry*; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D008024:Ligands; D008055:Lipids; D043562:Receptors, G-Protein-Coupled
keywords: GPCRs; ligand binding; lipidic cubic phase; protein engineering; structure-based drug discovery