National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM113164
米国
引用
ジャーナル: Open Biol / 年: 2023 タイトル: Nucleotide-free structures of KIF20A illuminate atypical mechanochemistry in this kinesin-6. 著者: Fanomezana Moutse Ranaivoson / Vincent Crozet / Matthieu P M H Benoit / Amna Abdalla Mohammed Khalid / Carlos Kikuti / Helena Sirkia / Ahmed El Marjou / Stéphanie Miserey-Lenkei / Ana B ...著者: Fanomezana Moutse Ranaivoson / Vincent Crozet / Matthieu P M H Benoit / Amna Abdalla Mohammed Khalid / Carlos Kikuti / Helena Sirkia / Ahmed El Marjou / Stéphanie Miserey-Lenkei / Ana B Asenjo / Hernando Sosa / Christoph F Schmidt / Steven S Rosenfeld / Anne Houdusse / 要旨: KIF20A is a critical kinesin for cell division and a promising anti-cancer drug target. The mechanisms underlying its cellular roles remain elusive. Interestingly, unusual coupling between the ...KIF20A is a critical kinesin for cell division and a promising anti-cancer drug target. The mechanisms underlying its cellular roles remain elusive. Interestingly, unusual coupling between the nucleotide- and microtubule-binding sites of this kinesin-6 has been reported, but little is known about how its divergent sequence leads to atypical motility properties. We present here the first high-resolution structure of its motor domain that delineates the highly unusual structural features of this motor, including a long L6 insertion that integrates into the core of the motor domain and that drastically affects allostery and ATPase activity. Together with the high-resolution cryo-electron microscopy microtubule-bound KIF20A structure that reveals the microtubule-binding interface, we dissect the peculiarities of the KIF20A sequence that influence its mechanochemistry, leading to low motility compared to other kinesins. Structural and functional insights from the KIF20A pre-power stroke conformation highlight the role of extended insertions in shaping the motor's mechanochemical cycle. Essential for force production and processivity is the length of the neck linker in kinesins. We highlight here the role of the sequence preceding the neck linker in controlling its backward docking and show that a neck linker four times longer than that in kinesin-1 is required for the activity of this motor.
回転角度/サブユニット: 168.09 ° / 軸方向距離/サブユニット: 5.62 Å / らせん対称軸の対称性: C1
粒子像の選択
詳細: manual picking of filaments
3次元再構成
解像度: 3.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 243559 詳細: Number of asymmetric units used is reported in "number of segments used", due to the local processing strategy employed. 対称性のタイプ: HELICAL