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.
想定した対称性 - らせんパラメータ - Δz: 5.62 Å 想定した対称性 - らせんパラメータ - ΔΦ: 168.09 ° 想定した対称性 - らせんパラメータ - 軸対称性: C1 (非対称) 解像度のタイプ: BY AUTHOR / 解像度: 3.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: RELION (ver. 3.1) 詳細: Number of asymmetric units used is reported in "number of segments used", due to the local processing strategy employed. 使用した粒子像数: 243559
Segment selection
詳細: manual picking of filaments
初期モデル
モデルのタイプ: OTHER
最終 角度割当
タイプ: NOT APPLICABLE / ソフトウェア - 名称: RELION (ver. 3.1)
FSC曲線 (解像度の算出)
-
原子モデル構築 1
精密化
空間: REAL / プロトコル: FLEXIBLE FIT
得られたモデル
PDB-8f1a: Apo KIF20A[1-565] class-1 in complex with a microtubule