Emerging Paradigm of Intracellular Targeting of G Protein-Coupled Receptors

被引:37
作者
Chaturvedi, Madhu [1 ]
Schilling, Justin [2 ]
Beautrait, Alexandre [3 ]
Bouvier, Michel [3 ,4 ]
Benovic, Jeffrey L. [2 ]
Shukla, Arun K. [1 ]
机构
[1] Indian Inst Technol, Dept Biol Sci & Bioengn, Kanpur 208016, Uttar Pradesh, India
[2] Thomas Jefferson Univ, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA
[3] Univ Montreal, IRIC, Montreal, PQ H3T 1J4, Canada
[4] Univ Montreal, Dept Biochem & Mol Med, Montreal, PQ H3T 1J4, Canada
基金
英国惠康基金; 美国国家卫生研究院;
关键词
CRYO-EM STRUCTURE; BETA-ARRESTIN; BINDING-SITE; STRUCTURAL INSIGHTS; GPCR; ACTIVATION; PEPDUCIN; IDENTIFICATION; ENDOCYTOSIS; ANTAGONISTS;
D O I
10.1016/j.tibs.2018.04.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
G protein-coupled receptors (GPCRs) recognize a diverse array of extracellular stimuli, and they mediate a broad repertoire of signaling events involved in human physiology. Although the major effort on targeting GPCRs has typically been focused on their extracellular surface, a series of recent developments now unfold the possibility of targeting them from the intracellular side as well. Allosteric modulators binding to the cytoplasmic surface of GPCRs have now been described, and their structural mechanisms are elucidated by high-resolution crystal structures. Furthermore, pepducins, aptamers, and intrabodies targeting the intracellular face of GPCRs have also been successfully utilized to modulate receptor signaling. Moreover, small molecule compounds, aptamers, and synthetic intrabodies targeting beta-arrestins have also been discovered to modulate GPCR endocytosis and signaling. Here, we discuss the emerging paradigm of intracellular targeting of GPCRs, and outline the current challenges, potential opportunities, and future outlook in this particular area of GPCR biology.
引用
收藏
页码:533 / 546
页数:14
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