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- PDB-8utv: KIF1A[1-393] P305L mutant ADP bound in complex with a microtubule -
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Open data
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Basic information
Entry | Database: PDB / ID: 8utv | ||||||||||||||||||
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Title | KIF1A[1-393] P305L mutant ADP bound in complex with a microtubule | ||||||||||||||||||
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![]() | MOTOR PROTEIN / KIF1A / kinesin / motility / microtubule / tubulin | ||||||||||||||||||
Function / homology | ![]() 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 / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / 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 Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3 Å | ||||||||||||||||||
![]() | Benoit, M.P.M.H. / Rao, L. / Asenjo, A.B. / Gennerich, A. / Sosa, H. | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM unveils kinesin KIF1A's processivity mechanism and the impact of its pathogenic variant P305L. Authors: Matthieu P M H Benoit / Lu Rao / Ana B Asenjo / Arne Gennerich / Hernando Sosa / ![]() Abstract: 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. | ||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 303.6 KB | Display | ![]() |
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PDB format | ![]() | 241.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 42551MC ![]() 8utnC ![]() 8utoC ![]() 8utpC ![]() 8utqC ![]() 8utrC ![]() 8utsC ![]() 8uttC ![]() 8utuC ![]() 8utwC ![]() 8utyC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 3 types, 4 molecules EABK
#1: Protein | Mass: 50204.445 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #2: Protein | | Mass: 49999.887 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #3: Protein | | Mass: 49304.480 Da / Num. of mol.: 1 / Fragment: residues 1-393 / Mutation: P305L Source method: isolated from a genetically manipulated source Details: leucine zipper from S. cerevisiae GCN4 at C-terminus Source: (gene. exp.) ![]() ![]() ![]() |
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-Non-polymers , 5 types, 7 molecules ![](data/chem/img/GTP.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/GDP.gif)
![](data/chem/img/TA1.gif)
![](data/chem/img/ADP.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/GDP.gif)
![](data/chem/img/TA1.gif)
![](data/chem/img/ADP.gif)
#4: Chemical | #5: Chemical | #6: Chemical | ChemComp-GDP / | #7: Chemical | ChemComp-TA1 / | #8: Chemical | ChemComp-ADP / | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
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Sample preparation
Component | Name: KIF1A[1-393] P305L mutant ADP in complex with a 15R microtubule Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES | ||||||||||||||||||||||||
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
Buffer solution | pH: 6.8 | ||||||||||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid type: UltrAuFoil | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 62.9 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Helical symmerty | Angular rotation/subunit: 168.09 ° / Axial rise/subunit: 5.45 Å / Axial symmetry: C1 |
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 119590 Details: Number of asymmetric units used is reported in "number of segments used", due to the local processing strategy employed. Symmetry type: HELICAL |