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| Title | Structural basis of mechano-chemical coupling by the mitotic kinesin KIF14. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 12, Issue 1, Page 3637, Year 2021 |
| Publish date | Jun 15, 2021 |
 Authors | Matthieu P M H Benoit / Ana B Asenjo / Mohammadjavad Paydar / Sabin Dhakal / Benjamin H Kwok / Hernando Sosa /   |
| PubMed Abstract | KIF14 is a mitotic kinesin whose malfunction is associated with cerebral and renal developmental defects and several cancers. Like other kinesins, KIF14 couples ATP hydrolysis and microtubule binding ...KIF14 is a mitotic kinesin whose malfunction is associated with cerebral and renal developmental defects and several cancers. Like other kinesins, KIF14 couples ATP hydrolysis and microtubule binding to the generation of mechanical work, but the coupling mechanism between these processes is still not fully clear. Here we report 20 high-resolution (2.7-3.9 Å) cryo-electron microscopy KIF14-microtubule structures with complementary functional assays. Analysis procedures were implemented to separate coexisting conformations of microtubule-bound monomeric and dimeric KIF14 constructs. The data provide a comprehensive view of the microtubule and nucleotide induced KIF14 conformational changes. It shows that: 1) microtubule binding, the nucleotide species, and the neck-linker domain govern the transition between three major conformations of the motor domain; 2) an undocked neck-linker prevents the nucleotide-binding pocket to fully close and dampens ATP hydrolysis; 3) 13 neck-linker residues are required to assume a stable docked conformation; 4) the neck-linker position controls the hydrolysis rather than the nucleotide binding step; 5) the two motor domains of KIF14 dimers adopt distinct conformations when bound to the microtubule; and 6) the formation of the two-heads-bound-state introduces structural changes in both motor domains of KIF14 dimers. These observations provide the structural basis for a coordinated chemo-mechanical kinesin translocation model. |
 External links | Nat Commun / PubMed:34131133 / PubMed Central |
| Methods | EM (helical sym.) |
| Resolution | 2.7 - 3.9 Å |
| Structure data | EMDB-21932, PDB-6wwe: EMDB-21933, PDB-6wwf: EMDB-21934, PDB-6wwg: EMDB-21935, PDB-6wwh: EMDB-21936, PDB-6wwi: EMDB-21937, PDB-6wwj: EMDB-21938, PDB-6wwk: EMDB-21939, PDB-6wwl: EMDB-21940, PDB-6wwm: EMDB-21941, PDB-6wwn: EMDB-21942, PDB-6wwo: EMDB-21943, PDB-6wwp: EMDB-21944, PDB-6wwq: EMDB-21945, PDB-6wwr: EMDB-21946, PDB-6wws: EMDB-21947, PDB-6wwt: EMDB-21948, PDB-6wwu: EMDB-21949, PDB-6wwv: EMDB-23540, PDB-7lvq: EMDB-23541, PDB-7lvr: |
| Chemicals |  ChemComp-GTP:  ChemComp-MG:  ChemComp-GDP:  ChemComp-TA1:  ChemComp-ADP:  ChemComp-AF3:  ChemComp-ANP: |
| Source |
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 Keywords |  MOTOR PROTEIN / KIF14 / kinesin / motility / microtubule / tubulin |
