Blog Archives

Hot topics: Intracellular allosteric antagonism of the CCR9 receptor

Chemokines and their GPCR receptors are important drug targets in a broad range of diseases due to their role in immune defence (by controlling migration, activation and survival of immune cells), viral entry, tumour growth and metastasis. This article presents

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Hot topics: Visualizing GPCR ‘Megaplexes’ Which Enable Sustained Intracellular Signaling

Spotlight article [1] discussing the range of cutting-edge techniques that have been employed to visualize ‘megaplexes’ consisting of a G protein-coupled receptor (GPCR) bound to β-arrestin in intracellular endosomes following agonist-induced internalization. Surprisingly, the complex includes simultaneous binding of the

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Hot topics: Structural basis for the gating mechanism of the type 2 ryanodine receptor RyR2

A report on the structures of type 2 ryanodine receptor from porcine heart at near-atomic resolution [1]. Structural and mutational characterisations provide important insights into the gating and disease mechanisms of RyR2. Guide to Pharmacology: Ryanodine receptor family. [1] Peng et

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Hot topics: The orphan GPR139 receptor is activated by peptides

GPR139 is an orphan class A G protein-coupled receptor found mainly in the central nervous system. It has its highest expression in the striatum and hypothalamus, regions regulating locomotion and metabolism, respectively, and it has therefore been suggested as a

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Hot topics: X-ray crystallographic study defines binding domains for Ca2+ antagonist drugs and their molecular mechanism of action

This year witnessed a tremendous progress in our understanding of the structure-function relationship of voltage-gated Ca2+ channels. This is based on the cryo-electron microscopy structure of the rabbit Cav1.1 Ca2+ channel complex at a nominal resolution of 3.6 Å ([1]

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Hot topics: Will the real splice variants please stand up?

The number of alternative mRNA splice forms that map to human protein coding loci has increased to the point that nearly all proteins have such associated database records. This gives rise to the paradox that the gene build pipeline from

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Hot topics: X-ray structure of the endothelin ETB receptor

Endothelin is a peptide that acts via two G-protein coupled receptors. ETA mainly causes vasoconstriction. In contrast ETB  predominantly acts as a beneficial clearing receptor and by the release of endothelium derived relaxing factors, vasodilatation [1,2]. This paper  describes for

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