#LactateReceptor
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plosbiology.org
The human #LactateReceptor HCAR1 is an emerging therapeutic target, but how does it work? This study reports the #cryoEM structure of HCAR1 in complex with heterotrimeric Gi1 protein to provide a structural framework for ligand recognition & receptor activation @plosbiology.org 🧪 plos.io/4ilzVqd
Top: Cryo-EM map and structural model of HCAR1-Gi1-scFv16 complex in the presence of CHBA (left) and apo form (second left). Cryo-EM maps and structural models of HCAR2-Gi1-scFv16 complex in the presence of MK-1903 (second right) and SCH900271 (right). The density of the agonist (shown as sticks) is depicted as gray meshes. The maps and structural models are colored by subunits. Bottom: Mechanism diagram of ligand recognition and selectivity of HCAR1. This study mainly showcases the HCAR1-Gi1 complexes in both the agonist-bound and apo forms, and the HCAR2-Gi1 complexes in the agonist-bound form. Four residues of HCAR1, namely R993.36, Y2687.43, E16645.51, and R712.60, are deemed crucial for ligand recognition. Notably, R993.36 undergoes a significant conformational change upon agonist binding. Furthermore, three residues in HCAR1/HCAR2, namely R71/L832.60, R79/W91ECL1, and Y75/Y872.64, play a decisive role in agonist selectivity between HCAR1 and HCAR2.
April 22, 2025 at 3:41 PM
plosbiology.org
The human #LactateReceptor HCAR1 is an emerging therapeutic target, but how does it work? This study reports the #cryoEM structure of HCAR1 in complex with heterotrimeric Gi1 protein to provide a structural framework for ligand recognition & receptor activation @plosbiology.org 🧪 plos.io/4ilzVqd
Top: Cryo-EM map and structural model of HCAR1-Gi1-scFv16 complex in the presence of CHBA (left) and apo form (second left). Cryo-EM maps and structural models of HCAR2-Gi1-scFv16 complex in the presence of MK-1903 (second right) and SCH900271 (right). The density of the agonist (shown as sticks) is depicted as gray meshes. The maps and structural models are colored by subunits. Bottom: Mechanism diagram of ligand recognition and selectivity of HCAR1. This study mainly showcases the HCAR1-Gi1 complexes in both the agonist-bound and apo forms, and the HCAR2-Gi1 complexes in the agonist-bound form. Four residues of HCAR1, namely R993.36, Y2687.43, E16645.51, and R712.60, are deemed crucial for ligand recognition. Notably, R993.36 undergoes a significant conformational change upon agonist binding. Furthermore, three residues in HCAR1/HCAR2, namely R71/L832.60, R79/W91ECL1, and Y75/Y872.64, play a decisive role in agonist selectivity between HCAR1 and HCAR2.
April 23, 2025 at 1:25 PM
plosbiology.org
The human #LactateReceptor HCAR1 is an emerging therapeutic target, but how does it work? This study reports the #cryoEM structure of HCAR1 in complex with heterotrimeric Gi1 protein to provide a structural framework for ligand recognition & receptor activation @plosbiology.org 🧪 plos.io/4ilzVqd
Top: Cryo-EM map and structural model of HCAR1-Gi1-scFv16 complex in the presence of CHBA (left) and apo form (second left). Cryo-EM maps and structural models of HCAR2-Gi1-scFv16 complex in the presence of MK-1903 (second right) and SCH900271 (right). The density of the agonist (shown as sticks) is depicted as gray meshes. The maps and structural models are colored by subunits. Bottom: Mechanism diagram of ligand recognition and selectivity of HCAR1. This study mainly showcases the HCAR1-Gi1 complexes in both the agonist-bound and apo forms, and the HCAR2-Gi1 complexes in the agonist-bound form. Four residues of HCAR1, namely R993.36, Y2687.43, E16645.51, and R712.60, are deemed crucial for ligand recognition. Notably, R993.36 undergoes a significant conformational change upon agonist binding. Furthermore, three residues in HCAR1/HCAR2, namely R71/L832.60, R79/W91ECL1, and Y75/Y872.64, play a decisive role in agonist selectivity between HCAR1 and HCAR2.
April 23, 2025 at 8:23 AM