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基本情報
登録情報 | データベース: PDB / ID: 8utu | |||||||||||||||||||||
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タイトル | KIF1A[1-393] P305L mutant AMP-PNP bound one and two heads bound states merged, in complex with a microtubule | |||||||||||||||||||||
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![]() | MOTOR PROTEIN / KIF1A / kinesin / motility / microtubule / tubulin | |||||||||||||||||||||
機能・相同性 | ![]() neuronal dense core vesicle membrane / dense core granule cytoskeletal transport / anterograde neuronal dense core vesicle transport / retrograde neuronal dense core vesicle transport / regulation of dendritic spine development / cytoskeleton-dependent intracellular transport / regulation of dendritic spine morphogenesis / anterograde axonal transport / Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / Hedgehog 'off' state ...neuronal dense core vesicle membrane / dense core granule cytoskeletal transport / anterograde neuronal dense core vesicle transport / retrograde neuronal dense core vesicle transport / regulation of dendritic spine development / cytoskeleton-dependent intracellular transport / regulation of dendritic spine morphogenesis / anterograde axonal transport / Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / Hedgehog 'off' state / Cilium Assembly / Intraflagellar transport / COPI-dependent Golgi-to-ER retrograde traffic / Carboxyterminal post-translational modifications of tubulin / RHOH GTPase cycle / Sealing of the nuclear envelope (NE) by ESCRT-III / Kinesins / PKR-mediated signaling / The role of GTSE1 in G2/M progression after G2 checkpoint / Aggrephagy / Resolution of Sister Chromatid Cohesion / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Separation of Sister Chromatids / Kinesins / plus-end-directed microtubule motor activity / RHO GTPases activate IQGAPs / RHO GTPases Activate Formins / Recruitment of NuMA to mitotic centrosomes / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / MHC class II antigen presentation / COPI-mediated anterograde transport / COPI-dependent Golgi-to-ER retrograde traffic / kinesin complex / microtubule-based movement / neuronal dense core vesicle / cytoskeletal motor activity / vesicle-mediated transport / axon cytoplasm / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / structural constituent of cytoskeleton / microtubule cytoskeleton organization / microtubule cytoskeleton / mitotic cell cycle / microtubule binding / microtubule / axon / GTPase activity / synapse / dendrite / GTP binding / perinuclear region of cytoplasm / ATP hydrolysis activity / ATP binding / identical protein binding / metal ion binding / cytoplasm 類似検索 - 分子機能 | |||||||||||||||||||||
生物種 | ![]() ![]() ![]() | |||||||||||||||||||||
手法 | 電子顕微鏡法 / らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 3 Å | |||||||||||||||||||||
![]() | Benoit, M.P.M.H. / Rao, L. / Asenjo, A.B. / Gennerich, A. / Sosa, H. | |||||||||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Cryo-EM unveils kinesin KIF1A's processivity mechanism and the impact of its pathogenic variant P305L. 著者: Matthieu P M H Benoit / Lu Rao / Ana B Asenjo / Arne Gennerich / Hernando Sosa / ![]() 要旨: Mutations in the microtubule-associated motor protein KIF1A lead to severe neurological conditions known as KIF1A-associated neurological disorders (KAND). Despite insights into its molecular ...Mutations in the microtubule-associated motor protein KIF1A lead to severe neurological conditions known as KIF1A-associated neurological disorders (KAND). Despite insights into its molecular mechanism, high-resolution structures of KIF1A-microtubule complexes remain undefined. Here, we present 2.7-3.5 Å resolution structures of dimeric microtubule-bound KIF1A, including the pathogenic P305L mutant, across various nucleotide states. Our structures reveal that KIF1A binds microtubules in one- and two-heads-bound configurations, with both heads exhibiting distinct conformations with tight inter-head connection. Notably, KIF1A's class-specific loop 12 (K-loop) forms electrostatic interactions with the C-terminal tails of both α- and β-tubulin. The P305L mutation does not disrupt these interactions but alters loop-12's conformation, impairing strong microtubule-binding. Structure-function analysis reveals the K-loop and head-head coordination as major determinants of KIF1A's superprocessive motility. Our findings advance the understanding of KIF1A's molecular mechanism and provide a basis for developing structure-guided therapeutics against KAND. | |||||||||||||||||||||
履歴 |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 348.6 KB | 表示 | ![]() |
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PDB形式 | ![]() | 275.6 KB | 表示 | ![]() |
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その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
関連構造データ | ![]() 42550MC ![]() 8utnC ![]() 8utoC ![]() 8utpC ![]() 8utqC ![]() 8utrC ![]() 8utsC ![]() 8uttC ![]() 8utvC ![]() 8utwC ![]() 8utyC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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要素
-タンパク質 , 3種, 4分子 KAEB
#1: タンパク質 | 分子量: 49304.480 Da / 分子数: 1 / 断片: residues 1-393 / 変異: P305L / 由来タイプ: 組換発現 詳細: "linker" residues are comprised of a leucine zipper based on S. cerevisiae GCN4, which is followed by the C-terminal strep-tag 由来: (組換発現) ![]() ![]() ![]() | ||
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#2: タンパク質 | 分子量: 50204.445 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #3: タンパク質 | | 分子量: 49999.887 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() |
-非ポリマー , 5種, 8分子 ![](data/chem/img/MG.gif)
![](data/chem/img/ANP.gif)
![](data/chem/img/GTP.gif)
![](data/chem/img/GDP.gif)
![](data/chem/img/TA1.gif)
![](data/chem/img/ANP.gif)
![](data/chem/img/GTP.gif)
![](data/chem/img/GDP.gif)
![](data/chem/img/TA1.gif)
#4: 化合物 | #5: 化合物 | ChemComp-ANP / | #6: 化合物 | #7: 化合物 | ChemComp-GDP / | #8: 化合物 | ChemComp-TA1 / | |
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-詳細
研究の焦点であるリガンドがあるか | N |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: FILAMENT / 3次元再構成法: らせん対称体再構成法 |
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試料調製
構成要素 | 名称: KIF1A[1-393] P305L mutant - AMP-PNP one and two-heads-bound states (merged) in complex with a 15R microtubule タイプ: COMPLEX / Entity ID: #1-#3 / 由来: MULTIPLE SOURCES | ||||||||||||||||||||||||
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分子量 | 実験値: NO | ||||||||||||||||||||||||
緩衝液 | pH: 6.8 | ||||||||||||||||||||||||
緩衝液成分 |
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試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||
試料支持 | グリッドのタイプ: UltrAuFoil | ||||||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2210 nm / 最小 デフォーカス(公称値): 810 nm |
撮影 | 電子線照射量: 49.36 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
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解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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らせん対称 | 回転角度/サブユニット: 168.09 ° / 軸方向距離/サブユニット: 5.64 Å / らせん対称軸の対称性: C1 |
3次元再構成 | 解像度: 3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 254197 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 |
精密化 | 最高解像度: 3 Å |