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Updated: Jul 12, 2025
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Assembling Molecular Shuttles Powered by Reversibly Attached Kinesins
Published on: January 26, 2019
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Autoinhibited kinesin-1 adopts a hierarchical folding pattern
Zhenyu Tan1,2, Yang Yue3, Felipe Leprevost4
1Department of Biophysics, University of Michigan, Ann Arbor, United States.
Elife
|November 1, 2023
Summary
Researchers uncovered the structure of autoinhibited kinesin-1, revealing a compact, bent conformation. Kinesin light chains stabilize this inhibited state, requiring multiple domain interactions to be disrupted for motor activation.
Area of Science:
- Cellular biology
- Molecular motors
- Structural biology
Background:
- Kinesin-1 is the main motor for anterograde transport of cellular cargo.
- The C-terminal tail of kinesin-1 is known to inhibit motility.
- The molecular structure of full-length autoinhibited kinesin-1 is not well understood.
Purpose of the Study:
- To determine the molecular architecture of full-length autoinhibited kinesin-1 homodimer and heterotetramer.
- To elucidate the role of kinesin light chains in the autoinhibition mechanism.
- To provide a structural basis for kinesin-1 activation.
Main Methods:
- Crosslinking mass spectrometry (XL-MS)
- Electron microscopy (EM)
- AlphaFold structure prediction
- Integrative structural analysis
Main Results:
- Kinesin-1 adopts a compact, bent conformation due to a break in coiled-coil 3.
- Kinesin light chains stabilize the existing inhibited state of kinesin-1.
- Activation of full-length kinesin-1 requires disrupting interactions across motor, stalk, and tail domains.
Conclusions:
- The study reveals the structural basis of kinesin-1 autoinhibition.
- Kinesin light chains play a stabilizing role in the inhibited state.
- A framework is provided for understanding how cargo adaptors and MAPs activate kinesin-1.
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