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-Structure paper
タイトル | The mechanochemical cycle of reactive full-length human dynein 1. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Year 2025 |
掲載日 | 2025年4月22日 |
![]() | Pengxin Chai / Jun Yang / Indigo C Geohring / Steven M Markus / Yue Wang / Kai Zhang / ![]() ![]() |
PubMed 要旨 | Dynein-driven cargo transport has a pivotal role in diverse cellular activities, central to which is dynein's mechanochemical cycle. Here, we performed a systematic cryo-electron microscopic ...Dynein-driven cargo transport has a pivotal role in diverse cellular activities, central to which is dynein's mechanochemical cycle. Here, we performed a systematic cryo-electron microscopic investigation of the conformational landscape of full-length human dynein 1 in reaction, in various nucleotide conditions, on and off microtubules. Our approach reveals over 40 high-resolution structures, categorized into eight states, providing a dynamic and comprehensive view of dynein throughout its mechanochemical cycle. The described intermediate states reveal mechanistic insights into dynein function, including a 'backdoor' phosphate release model that coordinates linker straightening, how microtubule binding enhances adenosine triphosphatase activity through a two-way communication mechanism and the crosstalk mechanism between AAA1 and the regulatory AAA3 site. Our findings also lead to a revised model for the force-generating powerstroke and reveal means by which dynein exhibits unidirectional stepping. These results improve our understanding of dynein and provide a more complete model of its mechanochemical cycle. |
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手法 | EM (単粒子) |
解像度 | 2.2 - 8.0 Å |
構造データ | EMDB-44681, PDB-9bly: EMDB-44682, PDB-9blz: EMDB-44683, PDB-9bm0: EMDB-44684, PDB-9bm1: EMDB-44685, PDB-9bm2: EMDB-44686, PDB-9bm3: EMDB-44687, PDB-9bm4: EMDB-44688, PDB-9bm5: EMDB-44689, PDB-9bm6: EMDB-44690, PDB-9bm7: EMDB-44691, PDB-9bm8: EMDB-44693, PDB-9bma: EMDB-44694, PDB-9bmb: EMDB-44695, PDB-9bmc: EMDB-44696, PDB-9bmd: EMDB-44697, PDB-9bmf: EMDB-44698, PDB-9bmg: EMDB-44699, PDB-9bmh: EMDB-44701, PDB-9bmj: EMDB-44702, PDB-9bml: EMDB-44703, PDB-9bmm: EMDB-44704, PDB-9bmn: EMDB-44705, PDB-9bmo: EMDB-44706, PDB-9bmp: EMDB-44708, PDB-9bmr: EMDB-44709, PDB-9bms: EMDB-44710, PDB-9bmt: EMDB-44711, PDB-9bmu: EMDB-44712, PDB-9bmv: EMDB-44713, PDB-9bmw: EMDB-44715, PDB-9bmy: EMDB-44716, PDB-9bmz: EMDB-44717, PDB-9bn0: EMDB-44718, PDB-9bn1: EMDB-44720, PDB-9bn3: EMDB-44721, PDB-9bn4: EMDB-44722, PDB-9bn5: EMDB-44723, PDB-9bn6: ![]() EMDB-46647: Raw consensus map of phi-particle dynein-1 ![]() EMDB-46648: Focused refinement map of tail region in phi-particle dynein-1 ![]() EMDB-46650: Focused refinement map of motor domain region in phi-particle dynein-1 EMDB-46856, PDB-9dh5: EMDB-46857, PDB-9dh6: EMDB-46858, PDB-9dh7: EMDB-46859, PDB-9dh8: EMDB-46860, PDB-9dh9: EMDB-46861, PDB-9dha: |
化合物 | ![]() ChemComp-ADP: ![]() ChemComp-ATP: ![]() ChemComp-MG: ![]() ChemComp-HOH: ![]() ChemComp-ANP: ![]() ChemComp-AOV: |
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![]() | MOTOR PROTEIN / dynein-1 / phi-particle |