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TitleHigh-resolution structures of kinesin on microtubules provide a basis for nucleotide-gated force-generation.
Journal, issue, pagesElife, Vol. 3, Page e04686, Year 2014
Publish dateNov 21, 2014
AuthorsZhiguo Shang / Kaifeng Zhou / Chen Xu / Roseann Csencsits / Jared C Cochran / Charles V Sindelar /
PubMed AbstractMicrotubule-based transport by the kinesin motors, powered by ATP hydrolysis, is essential for a wide range of vital processes in eukaryotes. We obtained insight into this process by developing ...Microtubule-based transport by the kinesin motors, powered by ATP hydrolysis, is essential for a wide range of vital processes in eukaryotes. We obtained insight into this process by developing atomic models for no-nucleotide and ATP states of the monomeric kinesin motor domain on microtubules from cryo-EM reconstructions at 5-6 Å resolution. By comparing these models with existing X-ray structures of ADP-bound kinesin, we infer a mechanistic scheme in which microtubule attachment, mediated by a universally conserved 'linchpin' residue in kinesin (N255), triggers a clamshell opening of the nucleotide cleft and accompanying release of ADP. Binding of ATP re-closes the cleft in a manner that tightly couples to translocation of cargo, via kinesin's 'neck linker' element. These structural transitions are reminiscent of the analogous nucleotide-exchange steps in the myosin and F1-ATPase motors and inform how the two heads of a kinesin dimer 'gate' each other to promote coordinated stepping along microtubules.
External linksElife / PubMed:25415053 / PubMed Central
MethodsEM (helical sym.)
Resolution5.0 Å
Structure data

EMDB-6187: High-resolution structures of kinesin on microtubules provide a basis for nucleotide-gated force generation
PDB-3j8x: High-resolution structure of no-nucleotide kinesin on microtubules
Method: EM (helical sym.) / Resolution: 5.0 Å

EMDB-6188: High-resolution structures of kinesin on microtubules provide a basis for nucleotide-gated force generation
PDB-3j8y: High-resolution structure of ATP analog-bound kinesin on microtubules
Method: EM (helical sym.) / Resolution: 5.0 Å

Chemicals

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
  • sus scrofa (pig)
KeywordsMOTOR PROTEIN/STRUCTURAL PROTEIN / molecular motors / kinesin / myosin / microtubules / cytoskeletal motors / MOTOR PROTEIN-STRUCTURAL PROTEIN complex

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