Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Cryo-EM unveils kinesin KIF1A's processivity mechanism and the impact of its pathogenic variant P305L.
Journal, issue, pages	Nat Commun, Vol. 15, Issue 1, Page 5530, Year 2024
Publish date	Jul 2, 2024
Authors	Matthieu P M H Benoit / Lu Rao / Ana B Asenjo / Arne Gennerich / Hernando Sosa /
PubMed 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.
External links	Nat Commun / PubMed:38956021 / PubMed Central
Methods	EM (helical sym.)
Resolution	2.7 - 3.4 Å
Structure data	42543 8utn EMDB-42543, PDB-8utn: KIF1A[1-393] AMP-PNP bound two-heads-bound state in complex with a microtubule (class T23L1) Method: EM (helical sym.) / Resolution: 3.1 Å 42544 8uto EMDB-42544, PDB-8uto: KIF1A[1-393] AMP-PNP bound two-heads-bound state in complex with a microtubule - class T2L1 Method: EM (helical sym.) / Resolution: 3.2 Å 42545 8utp EMDB-42545, PDB-8utp: KIF1A[1-393] - AMP-PNP two-heads-bound state in complex with a microtubule - class T3L1 Method: EM (helical sym.) / Resolution: 3.2 Å 42546 8utq EMDB-42546, PDB-8utq: KIF1A[1-393] AMP-PNP bound one-head-bound state in complex with a microtubule - class T1L02* Method: EM (helical sym.) / Resolution: 3.1 Å 42547 8utr EMDB-42547, PDB-8utr: KIF1A[1-393] ADP bound in complex with a microtubule Method: EM (helical sym.) / Resolution: 3.3 Å 42548 8uts EMDB-42548, PDB-8uts: KIF1A[1-393] APO in complex with a microtubule Method: EM (helical sym.) / Resolution: 2.7 Å 42549 8utt EMDB-42549, PDB-8utt: KIF1A[1-393] P305L mutant AMP-PNP bound two-heads-bound state in complex with a microtubule Method: EM (helical sym.) / Resolution: 3.1 Å 42550 8utu EMDB-42550: KIF1A[1-393] AMP-PNP bound one-head-bound state in complex with a microtubule - class T1L02* PDB-8utu: KIF1A[1-393] P305L mutant AMP-PNP bound one and two heads bound states merged, in complex with a microtubule Method: EM (helical sym.) / Resolution: 3.0 Å 42551 8utv EMDB-42551, PDB-8utv: KIF1A[1-393] P305L mutant ADP bound in complex with a microtubule Method: EM (helical sym.) / Resolution: 3.0 Å 42552 8utw EMDB-42552, PDB-8utw: KIF1A[1-393] P305L mutant APO in complex with a microtubule Method: EM (helical sym.) / Resolution: 3.4 Å 42553 8uty EMDB-42553, PDB-8uty: KIF1A[1-393] P364L mutant AMP-PNP bound two-heads-bound state in complex with a microtubule Method: EM (helical sym.) / Resolution: 3.3 Å
Chemicals	ChemComp-MG: Unknown entry ChemComp-ANP: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogueYM ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying moleculeYM ChemComp-GDP: GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying moleculeYM ChemComp-TA1: TAXOL / medication, chemotherapyYM ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM
Source	homo sapiens (human) sus scrofa (pig)
Keywords	MOTOR PROTEIN / KIF1A / kinesin / motility / microtubule / tubulin