Cryo-EM advances in GPCR structure determination
G-protein-coupled receptors (GPCRs) constitute a prominent superfamily in humans, and are categorized into six classes (A through F) that play indispensable roles in cellular communication and therapeutics. Nonetheless, their structural comprehension has been limited by challenges in high-resolution...
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| Vydané v: | Journal of biochemistry (Tokyo) Ročník 176; číslo 1; s. 1 |
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| Hlavní autori: | , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
England
01.07.2024
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| ISSN: | 1756-2651, 1756-2651 |
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| Abstract | G-protein-coupled receptors (GPCRs) constitute a prominent superfamily in humans, and are categorized into six classes (A through F) that play indispensable roles in cellular communication and therapeutics. Nonetheless, their structural comprehension has been limited by challenges in high-resolution data acquisition. This review highlights the transformative impact of cryogenic electron microscopy (cryo-EM) in the structural determinations of GPCR-G-protein complexes. Specific technologies such as nanobodies and mini-G-proteins stabilize complexes and facilitate structural determination. We discuss the structural alterations upon receptor activation in different GPCR classes, revealing their diverse mechanisms. These cryo-EM structures provide a robust foundation for comprehending GPCR function and pave the way for future breakthroughs in drug discovery and therapeutic targeting. |
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| AbstractList | G-protein-coupled receptors (GPCRs) constitute a prominent superfamily in humans, and are categorized into six classes (A through F) that play indispensable roles in cellular communication and therapeutics. Nonetheless, their structural comprehension has been limited by challenges in high-resolution data acquisition. This review highlights the transformative impact of cryogenic electron microscopy (cryo-EM) in the structural determinations of GPCR-G-protein complexes. Specific technologies such as nanobodies and mini-G-proteins stabilize complexes and facilitate structural determination. We discuss the structural alterations upon receptor activation in different GPCR classes, revealing their diverse mechanisms. These cryo-EM structures provide a robust foundation for comprehending GPCR function and pave the way for future breakthroughs in drug discovery and therapeutic targeting. G-protein-coupled receptors (GPCRs) constitute a prominent superfamily in humans and are categorized into six classes (A-F) that play indispensable roles in cellular communication and therapeutics. Nonetheless, their structural comprehension has been limited by challenges in high-resolution data acquisition. This review highlights the transformative impact of cryogenic electron microscopy (cryo-EM) on the structural determinations of GPCR-G-protein complexes. Specific technologies, such as nanobodies and mini-G-proteins, stabilize complexes and facilitate structural determination. We discuss the structural alterations upon receptor activation in different GPCR classes, revealing their diverse mechanisms. This review highlights the robust foundation for comprehending GPCR function and pave the way for future breakthroughs in drug discovery and therapeutic targeting.G-protein-coupled receptors (GPCRs) constitute a prominent superfamily in humans and are categorized into six classes (A-F) that play indispensable roles in cellular communication and therapeutics. Nonetheless, their structural comprehension has been limited by challenges in high-resolution data acquisition. This review highlights the transformative impact of cryogenic electron microscopy (cryo-EM) on the structural determinations of GPCR-G-protein complexes. Specific technologies, such as nanobodies and mini-G-proteins, stabilize complexes and facilitate structural determination. We discuss the structural alterations upon receptor activation in different GPCR classes, revealing their diverse mechanisms. This review highlights the robust foundation for comprehending GPCR function and pave the way for future breakthroughs in drug discovery and therapeutic targeting. |
| Author | Shihoya, Wataru Sano, Fumiya K Iwama, Aika Nureki, Osamu |
| Author_xml | – sequence: 1 givenname: Wataru surname: Shihoya fullname: Shihoya, Wataru organization: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan – sequence: 2 givenname: Aika surname: Iwama fullname: Iwama, Aika organization: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan – sequence: 3 givenname: Fumiya K surname: Sano fullname: Sano, Fumiya K organization: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan – sequence: 4 givenname: Osamu surname: Nureki fullname: Nureki, Osamu organization: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38498911$$D View this record in MEDLINE/PubMed |
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| Copyright | The Author(s) 2024. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved. |
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| Keywords | Cryo-EM Structural biology G-protein-coupled receptor |
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