Introduction
Introduction
The G protein-coupled receptor (GPCR) family is the largest family of membrane proteins in eukaryotes. It encodes at least 800 human genes. But endogenous ligands of more than 140 GPCRs have not been determined. Such GPCRs are referred to as orphan GPCRs (oGPCRs). A variety of extracellular signals or specific ligands can bind to GPCRs, activate G-protein heterotrimers and downstream second messengers. They play an important role in a variety of physiological and pathological processes such as behavior, vision and tumorigenesis.
GPCR Structure
The GPCR has seven transmembrane α-helical stereostructures. The amino terminus of the peptide chain is located outside the membrane, and the carboxy terminus is located in the cytoplasm. A G protein (guanylate binding protein) binding site is present at the cytoplasmic ends of the fifth and sixth transmembrane helices and the carboxy terminus of the peptide chain. According to sequence similarity, GPCRs are mainly divided into four types: a class A rhodopsin receptor, a class B secretin receptor, a class C metabotropic glutamate receptor, and a class D Frizzled receptor. Due to the special structure of GPCRs, the diversity of signal mechanisms and the diversification of functions, 30%~50% of drugs on the market currently target GPCRs and their coupled downstream signaling molecules, but there are relatively few targeted drugs for treating tumors based on GPCRs.
The G protein-coupled receptor (GPCR) family is the largest family of membrane proteins in eukaryotes. It encodes at least 800 human genes. But endogenous ligands of more than 140 GPCRs have not been determined. Such GPCRs are referred to as orphan GPCRs (oGPCRs). A variety of extracellular signals or specific ligands can bind to GPCRs, activate G-protein heterotrimers and downstream second messengers. They play an important role in a variety of physiological and pathological processes such as behavior, vision and tumorigenesis.
GPCR Structure
The GPCR has seven transmembrane α-helical stereostructures. The amino terminus of the peptide chain is located outside the membrane, and the carboxy terminus is located in the cytoplasm. A G protein (guanylate binding protein) binding site is present at the cytoplasmic ends of the fifth and sixth transmembrane helices and the carboxy terminus of the peptide chain. According to sequence similarity, GPCRs are mainly divided into four types: a class A rhodopsin receptor, a class B secretin receptor, a class C metabotropic glutamate receptor, and a class D Frizzled receptor. Due to the special structure of GPCRs, the diversity of signal mechanisms and the diversification of functions, 30%~50% of drugs on the market currently target GPCRs and their coupled downstream signaling molecules, but there are relatively few targeted drugs for treating tumors based on GPCRs.
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