4RH7

Crystal structure of human cytoplasmic dynein 2 motor domain in complex with ADP.Vi

4RH7 の概要

• エントリーDOI: 10.2210/pdb4rh7/pdb
• 分子名称: Green fluorescent protein/Cytoplasmic dynein 2 heavy chain 1, ADP ORTHOVANADATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: aaa+ protein, motor protein, dynein motor domain
• 由来する生物種: synthetic construct (artificial gene, human); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton, cilium axoneme : Q8NCM8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 394917.44

構造登録者

Schmidt, H.,Zalyte, R.,Urnavicius, L.,Carter, A.P. (登録日: 2014-10-01, 公開日: 2014-12-10, 最終更新日: 2024-02-28)

主引用文献

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

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: 25470043
DOI: 10.1038/nature14023

実験手法

X-RAY DIFFRACTION (3.41 Å)