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-Structure paper
タイトル | Full-Length P2X Structures Reveal How Palmitoylation Prevents Channel Desensitization. |
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ジャーナル・号・ページ | Cell, Vol. 179, Issue 3, Page 659-670.e13, Year 2019 |
掲載日 | 2019年10月17日 |
![]() | Alanna E McCarthy / Craig Yoshioka / Steven E Mansoor / ![]() |
PubMed 要旨 | P2X receptors are trimeric, non-selective cation channels activated by extracellular ATP. The P2X receptor subtype is a pharmacological target because of involvement in apoptotic, inflammatory, and ...P2X receptors are trimeric, non-selective cation channels activated by extracellular ATP. The P2X receptor subtype is a pharmacological target because of involvement in apoptotic, inflammatory, and tumor progression pathways. It is the most structurally and functionally distinct P2X subtype, containing a unique cytoplasmic domain critical for the receptor to initiate apoptosis and not undergo desensitization. However, lack of structural information about the cytoplasmic domain has hindered understanding of the molecular mechanisms underlying these processes. We report cryoelectron microscopy structures of full-length rat P2X receptor in apo and ATP-bound states. These structures reveal how one cytoplasmic element, the C-cys anchor, prevents desensitization by anchoring the pore-lining helix to the membrane with palmitoyl groups. They show a second cytoplasmic element with a unique fold, the cytoplasmic ballast, which unexpectedly contains a zinc ion complex and a guanosine nucleotide binding site. Our structures provide first insights into the architecture and function of a P2X receptor cytoplasmic domain. |
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手法 | EM (単粒子) |
解像度 | 2.9 - 3.3 Å |
構造データ | EMDB-20702: EMDB: Cryo electron microscopy map of the ATP-gated rat P2X7 ion channel in the apo, closed state EMDB-20703: Cryo electron microscopy map of the ATP-gated rat P2X7 ion channel in the ATP-bound, open state |
化合物 | ![]() ChemComp-GDP: ![]() ChemComp-ZN: ![]() ChemComp-NAG: ![]() ChemComp-Q3G: ![]() ChemComp-PLM: ![]() ChemComp-ATP: |
由来 |
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![]() | MEMBRANE PROTEIN / Ion Channel Apoptosis |