Multiple recent HCAR2 structures demonstrate a highly dynamic ligand binding and G protein activation mode

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Multiple recent HCAR2 structures demonstrate a highly dynamic ligand binding and G protein activation mode. / Shenol, Aslihan; Tenente, Ricardo; Lückmann, Michael; Frimurer, Thomas M.; Schwartz, Thue W.

In: Nature Communications, Vol. 15, 5364, 2024.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Shenol, A, Tenente, R, Lückmann, M, Frimurer, TM & Schwartz, TW 2024, 'Multiple recent HCAR2 structures demonstrate a highly dynamic ligand binding and G protein activation mode', Nature Communications, vol. 15, 5364. https://doi.org/10.1038/s41467-024-49536-y

APA

Shenol, A., Tenente, R., Lückmann, M., Frimurer, T. M., & Schwartz, T. W. (2024). Multiple recent HCAR2 structures demonstrate a highly dynamic ligand binding and G protein activation mode. Nature Communications, 15, [5364]. https://doi.org/10.1038/s41467-024-49536-y

Vancouver

Shenol A, Tenente R, Lückmann M, Frimurer TM, Schwartz TW. Multiple recent HCAR2 structures demonstrate a highly dynamic ligand binding and G protein activation mode. Nature Communications. 2024;15. 5364. https://doi.org/10.1038/s41467-024-49536-y

Author

Shenol, Aslihan ; Tenente, Ricardo ; Lückmann, Michael ; Frimurer, Thomas M. ; Schwartz, Thue W. / Multiple recent HCAR2 structures demonstrate a highly dynamic ligand binding and G protein activation mode. In: Nature Communications. 2024 ; Vol. 15.

Bibtex

@article{de6ad69096a7444dabaa5a384cd1d262,
title = "Multiple recent HCAR2 structures demonstrate a highly dynamic ligand binding and G protein activation mode",
abstract = "A surprisingly clear picture of the allosteric mechanism connecting G protein-coupled receptor agonists with G protein binding—and back – is revealed by a puzzle of thirty novel 3D structures of the hydroxycarboxylic acid receptor 2 (HCAR2) in complex with eight different orthosteric and a single allosteric agonist. HCAR2 is a sensor of β-hydroxybutyrate, niacin and certain anti-inflammatory drugs. Surprisingly, agonists with and without on-target side effects bound very similarly and in a completely occluded orthosteric binding site. Thus, despite the many structures we are still left with a pertinent need to understand the molecular dynamics of this and similar systems.",
author = "Aslihan Shenol and Ricardo Tenente and Michael L{\"u}ckmann and Frimurer, {Thomas M.} and Schwartz, {Thue W.}",
note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",
year = "2024",
doi = "10.1038/s41467-024-49536-y",
language = "English",
volume = "15",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Multiple recent HCAR2 structures demonstrate a highly dynamic ligand binding and G protein activation mode

AU - Shenol, Aslihan

AU - Tenente, Ricardo

AU - Lückmann, Michael

AU - Frimurer, Thomas M.

AU - Schwartz, Thue W.

N1 - Publisher Copyright: © The Author(s) 2024.

PY - 2024

Y1 - 2024

N2 - A surprisingly clear picture of the allosteric mechanism connecting G protein-coupled receptor agonists with G protein binding—and back – is revealed by a puzzle of thirty novel 3D structures of the hydroxycarboxylic acid receptor 2 (HCAR2) in complex with eight different orthosteric and a single allosteric agonist. HCAR2 is a sensor of β-hydroxybutyrate, niacin and certain anti-inflammatory drugs. Surprisingly, agonists with and without on-target side effects bound very similarly and in a completely occluded orthosteric binding site. Thus, despite the many structures we are still left with a pertinent need to understand the molecular dynamics of this and similar systems.

AB - A surprisingly clear picture of the allosteric mechanism connecting G protein-coupled receptor agonists with G protein binding—and back – is revealed by a puzzle of thirty novel 3D structures of the hydroxycarboxylic acid receptor 2 (HCAR2) in complex with eight different orthosteric and a single allosteric agonist. HCAR2 is a sensor of β-hydroxybutyrate, niacin and certain anti-inflammatory drugs. Surprisingly, agonists with and without on-target side effects bound very similarly and in a completely occluded orthosteric binding site. Thus, despite the many structures we are still left with a pertinent need to understand the molecular dynamics of this and similar systems.

U2 - 10.1038/s41467-024-49536-y

DO - 10.1038/s41467-024-49536-y

M3 - Journal article

C2 - 38918366

AN - SCOPUS:85196845948

VL - 15

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 5364

ER -

ID: 396637618