4RH7
Crystal structure of human cytoplasmic dynein 2 motor domain in complex with ADP.Vi
Summary for 4RH7
| Entry DOI | 10.2210/pdb4rh7/pdb |
| Descriptor | Green fluorescent protein/Cytoplasmic dynein 2 heavy chain 1, ADP ORTHOVANADATE, MAGNESIUM ION, ... (5 entities in total) |
| Functional Keywords | aaa+ protein, motor protein, dynein motor domain |
| Biological source | synthetic construct (artificial gene, human) More |
| Cellular location | Cytoplasm, cytoskeleton, cilium axoneme : Q8NCM8 |
| Total number of polymer chains | 1 |
| Total formula weight | 394917.44 |
| Authors | Schmidt, H.,Zalyte, R.,Urnavicius, L.,Carter, A.P. (deposition date: 2014-10-01, release date: 2014-12-10, Last modification date: 2024-02-28) |
| Primary citation | Schmidt, H.,Zalyte, R.,Urnavicius, L.,Carter, A.P. Structure of human cytoplasmic dynein-2 primed for its power stroke. Nature, 518:435-438, 2015 Cited by PubMed Abstract: Members of the dynein family, consisting of cytoplasmic and axonemal isoforms, are motors that move towards the minus ends of microtubules. Cytoplasmic dynein-1 (dynein-1) plays roles in mitosis and cellular cargo transport, and is implicated in viral infections and neurodegenerative diseases. Cytoplasmic dynein-2 (dynein-2) performs intraflagellar transport and is associated with human skeletal ciliopathies. Dyneins share a conserved motor domain that couples cycles of ATP hydrolysis with conformational changes to produce movement. Here we present the crystal structure of the human cytoplasmic dynein-2 motor bound to the ATP-hydrolysis transition state analogue ADP.vanadate. The structure reveals a closure of the motor's ring of six AAA+ domains (ATPases associated with various cellular activites: AAA1-AAA6). This induces a steric clash with the linker, the key element for the generation of movement, driving it into a conformation that is primed to produce force. Ring closure also changes the interface between the stalk and buttress coiled-coil extensions of the motor domain. This drives helix sliding in the stalk which causes the microtubule binding domain at its tip to release from the microtubule. Our structure answers the key questions of how ATP hydrolysis leads to linker remodelling and microtubule affinity regulation. PubMed: 25470043DOI: 10.1038/nature14023 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.41 Å) |
Structure validation
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