4UXR

Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins

Summary for 4UXR

• Entry DOI: 10.2210/pdb4uxr/pdb
• Related: 4UXO 4UXP 4UXS 4UXT 4UXY 4UY0
• EMDB information: 2767
• Descriptor: TUBULIN ALPHA-1B CHAIN, TETRAFLUOROALUMINATE ION, TUBULIN BETA-2B CHAIN, ... (10 entities in total)
• Functional Keywords: transport protein, microtubule
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm, cytoskeleton: P81947 Q6B856 Q12756
• Total number of polymer chains: 3
• Total formula weight: 144567.74

Authors

Atherton, J.,Farabella, I.,Yu, I.M.,Rosenfeld, S.S.,Houdusse, A.,Topf, M.,Moores, C. (deposition date: 2014-08-27, release date: 2014-09-24, Last modification date: 2024-05-08)

Primary citation

Atherton, J.,Farabella, I.,Yu, I.,Rosenfeld, S.S.,Houdusse, A.,Topf, M.,Moores, C.A.
Conserved Mechanisms of Microtubule-Stimulated Adp Release, ATP Binding, and Force Generation in Transport Kinesins.
Elife, 3:3680-, 2014

PubMed Abstract: Kinesins are a superfamily of microtubule-based ATP-powered motors, important for multiple, essential cellular functions. How microtubule binding stimulates their ATPase and controls force generation is not understood. To address this fundamental question, we visualized microtubule-bound kinesin-1 and kinesin-3 motor domains at multiple steps in their ATPase cycles--including their nucleotide-free states--at ∼ 7 Å resolution using cryo-electron microscopy. In both motors, microtubule binding promotes ordered conformations of conserved loops that stimulate ADP release, enhance microtubule affinity and prime the catalytic site for ATP binding. ATP binding causes only small shifts of these nucleotide-coordinating loops but induces large conformational changes elsewhere that allow force generation and neck linker docking towards the microtubule plus end. Family-specific differences across the kinesin-microtubule interface account for the distinctive properties of each motor. Our data thus provide evidence for a conserved ATP-driven mechanism for kinesins and reveal the critical mechanistic contribution of the microtubule interface.

PubMed: 25209998
DOI: 10.7554/ELIFE.03680

Experimental method

ELECTRON MICROSCOPY (7 Å)