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-Structure paper
タイトル | Structures of human Na1.7 channel in complex with auxiliary subunits and animal toxins. |
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ジャーナル・号・ページ | Science, Vol. 363, Issue 6433, Page 1303-1308, Year 2019 |
掲載日 | 2019年3月22日 |
![]() | Huaizong Shen / Dongliang Liu / Kun Wu / Jianlin Lei / Nieng Yan / ![]() |
PubMed 要旨 | Voltage-gated sodium channel Na1.7 represents a promising target for pain relief. Here we report the cryo-electron microscopy structures of the human Na1.7-β1-β2 complex bound to two combinations ...Voltage-gated sodium channel Na1.7 represents a promising target for pain relief. Here we report the cryo-electron microscopy structures of the human Na1.7-β1-β2 complex bound to two combinations of pore blockers and gating modifier toxins (GMTs), tetrodotoxin with protoxin-II and saxitoxin with huwentoxin-IV, both determined at overall resolutions of 3.2 angstroms. The two structures are nearly identical except for minor shifts of voltage-sensing domain II (VSD), whose S3-S4 linker accommodates the two GMTs in a similar manner. One additional protoxin-II sits on top of the S3-S4 linker in VSD The structures may represent an inactivated state with all four VSDs "up" and the intracellular gate closed. The structures illuminate the path toward mechanistic understanding of the function and disease of Na1.7 and establish the foundation for structure-aided development of analgesics. |
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手法 | EM (単粒子) |
解像度 | 3.2 Å |
構造データ | EMDB-9781: Structure of human voltage-gated sodium channel Nav1.7 in complex with auxiliary beta subunits, huwentoxin-IV and saxitoxin EMDB-9782: Structure of human voltage-gated sodium channel Nav1.7 in complex with auxiliary beta subunits, ProTx-II and tetrodotoxin |
化合物 | ![]() ChemComp-NAG: ![]() ChemComp-9SL: ![]() ChemComp-9SR: |
由来 |
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![]() | MEMBRANE PROTEIN / voltage-gated sodium channel |