TY - JOUR
T1 - Successful Strategies to Determine High-Resolution Structures of GPCRs
AU - Xiang, Jin
AU - Chun, Eugene
AU - Liu, Chang
AU - Jing, Liang
AU - Al-Sahouri, Zina
AU - Zhu, Lan
AU - Liu, Wei
N1 - Funding Information:
This work was supported by the NSF STC award 1231306, a Mayo Clinic-ASU Collaborative Seed Grant Award, and the Flinn Foundation.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
KW - GPCRs
KW - ligand binding
KW - lipidic cubic phase
KW - protein engineering
KW - structure-based drug discovery
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U2 - 10.1016/j.tips.2016.09.009
DO - 10.1016/j.tips.2016.09.009
M3 - Review article
C2 - 27726881
AN - SCOPUS:84992170625
SN - 0165-6147
VL - 37
SP - 1055
EP - 1069
JO - Trends in Pharmacological Sciences
JF - Trends in Pharmacological Sciences
IS - 12
ER -