5LT2

nucleotide-free kinesin-1 motor domain, P1 crystal form

Summary for 5LT2

• Entry DOI: 10.2210/pdb5lt2/pdb
• Descriptor: Kinesin-like protein, SULFATE ION (3 entities in total)
• Functional Keywords: kinesin motor domain, adp dissociation, nucleotide-free, motor protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 6
• Total formula weight: 218717.17

Authors

Cao, L.,Gigant, B. (deposition date: 2016-09-06, release date: 2017-03-01, Last modification date: 2024-01-17)

Primary citation

Cao, L.,Cantos-Fernandes, S.,Gigant, B.
The structural switch of nucleotide-free kinesin.
Sci Rep, 7:42558-42558, 2017

PubMed Abstract: Kinesin-1 is an ATP-dependent motor protein that moves towards microtubules (+)-ends. Whereas structures of isolated ADP-kinesin and of complexes with tubulin of apo-kinesin and of ATP-like-kinesin are available, structural data on apo-kinesin-1 in the absence of tubulin are still missing, leaving the role of nucleotide release in the structural cycle unsettled. Here, we identified mutations in the kinesin nucleotide-binding P-loop motif that interfere with ADP binding. These mutations destabilize the P-loop (T87A mutant) or magnesium binding (T92V), highlighting a dual mechanism for nucleotide release. The structures of these mutants in their apo form are either isomorphous to ADP-kinesin-1 or to tubulin-bound apo-kinesin-1. Remarkably, both structures are also obtained from the nucleotide-depleted wild-type protein. Our results lead to a model in which, when detached from microtubules, apo-kinesin possibly occupies the two conformations we characterized, whereas, upon microtubule binding, ADP-kinesin converts to the tubulin-bound apo-kinesin conformation and releases ADP. This conformation is primed to bind ATP and, therefore, to run through the natural nucleotide cycle of kinesin-1.

PubMed: 28195215
DOI: 10.1038/srep42558

Experimental method

X-RAY DIFFRACTION (2.6 Å)