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-Structure paper
タイトル | Structural basis of purine nucleotide inhibition of human uncoupling protein 1. |
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ジャーナル・号・ページ | Sci Adv, Vol. 9, Issue 22, Page eadh4251, Year 2023 |
掲載日 | 2023年6月2日 |
著者 | Scott A Jones / Prerana Gogoi / Jonathan J Ruprecht / Martin S King / Yang Lee / Thomas Zögg / Els Pardon / Deepak Chand / Stefan Steimle / Danielle M Copeman / Camila A Cotrim / Jan Steyaert / Paul G Crichton / Vera Moiseenkova-Bell / Edmund R S Kunji / |
PubMed 要旨 | Mitochondrial uncoupling protein 1 (UCP1) gives brown adipose tissue of mammals its specialized ability to burn calories as heat for thermoregulation. When activated by fatty acids, UCP1 catalyzes ...Mitochondrial uncoupling protein 1 (UCP1) gives brown adipose tissue of mammals its specialized ability to burn calories as heat for thermoregulation. When activated by fatty acids, UCP1 catalyzes the leak of protons across the mitochondrial inner membrane, short-circuiting the mitochondrion to generate heat, bypassing ATP synthesis. In contrast, purine nucleotides bind and inhibit UCP1, regulating proton leak by a molecular mechanism that is unclear. We present the cryo-electron microscopy structure of the GTP-inhibited state of UCP1, which is consistent with its nonconducting state. The purine nucleotide cross-links the transmembrane helices of UCP1 with an extensive interaction network. Our results provide a structural basis for understanding the specificity and pH dependency of the regulatory mechanism. UCP1 has retained all of the key functional and structural features required for a mitochondrial carrier-like transport mechanism. The analysis shows that inhibitor binding prevents the conformational changes that UCP1 uses to facilitate proton leak. |
リンク | Sci Adv / PubMed:37256948 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.8 Å |
構造データ | EMDB-29857, PDB-8g8w: |
化合物 | ChemComp-GTP: ChemComp-CDL: |
由来 |
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キーワード | MEMBRANE PROTEIN / SLC25 / mitochondrial carrier / uncoupling |