Molecular insights into the atypical activation mechanism of GPR156 in maintaining auditory function
Abstract The class C orphan GPCR GPR156, which lacks the typical extracellular region, plays a pivotal role in auditory function through Gi2/3. Here, we demonstrate that GPR156 with high constitutive activity is essential for maintaining auditory function, and we further present two cryo-EM structures of human GPR156. The GPR156 dimer in both the apo state and Gi3protein-coupled state adopt a TM5/6-TM5/6 interface, indicating the high constitutive activity of GPR156 in the apo state. The C-terminus plays a dual role in promoting G protein binding within G-bound subunit while preventing the G-free subunit from binding to additional G protein. These observations explain how GPCR activity is maintained through dimerization and provide a mechanistic insight into the sustained role of GPR156 in maintaining auditory function..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 12. März Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ma, Xiangyu [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2024.03.07.581839 |
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| PPN (Katalog-ID): |
XBI042843324 |
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| 245 | 1 | 0 | |a Molecular insights into the atypical activation mechanism of GPR156 in maintaining auditory function |
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| 520 | |a Abstract The class C orphan GPCR GPR156, which lacks the typical extracellular region, plays a pivotal role in auditory function through Gi2/3. Here, we demonstrate that GPR156 with high constitutive activity is essential for maintaining auditory function, and we further present two cryo-EM structures of human GPR156. The GPR156 dimer in both the apo state and Gi3protein-coupled state adopt a TM5/6-TM5/6 interface, indicating the high constitutive activity of GPR156 in the apo state. The C-terminus plays a dual role in promoting G protein binding within G-bound subunit while preventing the G-free subunit from binding to additional G protein. These observations explain how GPCR activity is maintained through dimerization and provide a mechanistic insight into the sustained role of GPR156 in maintaining auditory function. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Chen, Li-Nan |4 aut | |
| 700 | 1 | |a Liao, Menghui |4 aut | |
| 700 | 1 | |a Zhang, Liyan |4 aut | |
| 700 | 1 | |a Xi, Kun |4 aut | |
| 700 | 1 | |a Guo, Jiamin |4 aut | |
| 700 | 1 | |a Shen, Cangsong |4 aut | |
| 700 | 1 | |a Shen, Dan-Dan |4 aut | |
| 700 | 1 | |a Cai, Pengjun |4 aut | |
| 700 | 1 | |a Shen, Qingya |4 aut | |
| 700 | 1 | |a Qi, Jieyu |4 aut | |
| 700 | 1 | |a Zhang, Huibing |4 aut | |
| 700 | 1 | |a Zang, Shao-Kun |4 aut | |
| 700 | 1 | |a Dong, Ying-Jun |4 aut | |
| 700 | 1 | |a Miao, Luwei |4 aut | |
| 700 | 1 | |a Qin, Jiao |4 aut | |
| 700 | 1 | |a Ji, Su-Yu |4 aut | |
| 700 | 1 | |a Li, Yue |4 aut | |
| 700 | 1 | |a Liu, Jianfeng |4 aut | |
| 700 | 1 | |a Mao, Chunyou |4 aut | |
| 700 | 1 | |a Zhang, Yan |4 aut | |
| 700 | 1 | |a Chai, Renjie |4 aut | |
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