#gpcrs

#Lysophosphatidylserine is a lipid signalling molecule implicated in a range of #immune-related processes. This study reveals the mechanism of #LysoPS recognition by two #GPCRs, GPR34 & GPR174, with implications for drug discovery #PLOSBiology https://plos.io/3T9ryVM

Some of my colleagues at Schrödinger recently published a preprint on a robust protocol to dock ligands into GPCR structures (or Alphafold models) and wrote a blog post about it.

Blog post:
https://extrapolations.com/can-alphafold-models-be-used-for-structure-based-drug-design-a-perspective-two-years-in/

Preprint:
https://chemrxiv.org/engage/chemrxiv/article-details/64caab6edfabaf06ff98c583

#GPCRs #Docking #AlphaFold2

First preprint about my work at Schrödinger:

We show how to predict ligand efficacy via absolute binding free energy perturbation on different receptor conformations — confirming and utilizing the principle that the functional response of a receptor is mainly determined by the thermodynamics of ligand binding.

https://chemrxiv.org/engage/chemrxiv/article-details/64b1cccaae3d1a7b0db45aa8

#FEP #FreeEnergy #LigandEfficacy #GPCR #DrugDiscovery #DrugDesign #Thermodynamics #GPCRs #BindingFreeEnergy

The 31 new deorphanized #neuropeptide #GPCRs from #Nematostella and the #phylogenetic trees also allowed us to predict the ligand for many receptors across #cnidarians. We hope that cnidarian researchers will functionally characterising these e.g. by #CRISPR, as the Houliston lab has done for the MIH receptor.
https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000614
#evolution #neuroscience

By phylogenetic reconstruction, Daniel Thiel and Luis Yanez could show that #cnidarian #neuropeptide receptors diversified independent from #GPCRs in bilateria. This parallel #evolution and expansion confirms that cnidarians do not represent the ancestral state in neuronal signalling (as implied by terms like 'pre-bilaterian') any more than bilaterians.
#receptor #evolution #neuroscience #phylogeny

In the Editors' Choice piece in Science Signaling, I highlight a nice study by Grimes et al. in Cell that shows that the protein beta-arrestin preassociates with the plasma membrane, facilitating its interaction with GPCRs and its activation. After transiently interacting in response to ligand, both GPCRs and arrestins travel independently to clathrin-coated pits, where they again interact to enable receptor internalization. Read my summary here: https://www.science.org/doi/10.1126/scisignal.adj0071 #GPCRs #biochemistry

In the new issue of Science Signaling, Hewitt et al. investigated the role of a conserved catalytic glutamine residue in G protein alpha-subunits, which mediates G protein inactivation. Mutations at this site in some G proteins lead to constitutive activity and oncogenesis. However, the authors found that other mutations of this residue led to multiple active state conformations, suggesting that this residue goes beyond catalysis to regulate structure and function. https://www.science.org/doi/10.1126/scisignal.abq7842 #GPCRs

@FlorianMerkle Welcome to the #CiliaFediverse Florian- we are glad your are here! #cilia #obesity #GPCRs #ciliopathies #neurons