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Related Experiment Video

Updated: Sep 28, 2025

Characterizing the Composition of Molecular Motors on Moving Axonal Cargo Using "Cargo Mapping" Analysis
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AAA+ proteins: one motor, multiple ways to work.

JiaBei Lin1, James Shorter1, Aaron L Lucius2

  • 1Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, U.S.A.

Biochemical Society Transactions
|March 31, 2022
PubMed
Summary

AAA+ proteins are molecular motors that translocate substrates. This review examines experimental methods to understand their diverse translocation mechanisms, suggesting motors can switch mechanisms for efficiency.

Keywords:
AAA+ClpAClpBHsp104clpx

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • ATPases associated with diverse cellular activities (AAA+) proteins are hexameric ring-like complexes.
  • These motors translocate substrates through a central channel via ATP hydrolysis.
  • Previous studies suggest a sequential 2-residue translocation model based on cryo-EM structures.

Purpose of the Study:

  • To review experimental methods for studying AAA+ motor translocation in solution.
  • To investigate if structurally similar AAA+ motors employ different translocation mechanisms.
  • To explore the possibility of single AAA+ motors utilizing multiple translocation mechanisms.

Main Methods:

  • Review of experimental techniques for solution-based analysis of AAA+ motor function.
  • Comparative analysis of translocation mechanisms across different AAA+ proteins (Hsp104, ClpB, ClpA, ClpX).
  • Discussion of structural similarities and mechanistic diversity among AAA+ motors.

Main Results:

  • Experimental determination of translocation properties is lacking for many AAA+ proteins.
  • A precise two-residue translocation step-size has not been consistently resolved.
  • AAA+ motors may possess multiple translocation mechanisms.

Conclusions:

  • Structurally similar AAA+ motors might employ distinct translocation mechanisms.
  • A single AAA+ motor could adapt its mechanism based on substrate or environmental challenges.
  • AAA+ motors likely switch to the most energetically efficient mechanism under constraint.