A physical model reveals the mechanochemistry responsible for Dynein's processive motion

Denis Tsygankov, Adrian W R Serohijos, Nikolay Dokholyan, Timothy C. Elston

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The molecular motor dynein is associated with various cellular activities, such as directed transport along microtubules and the rhythmic beating of the axoneme. Because of the size and complexity of the protein, a detailed understanding of the mechanochemistry that drives dynein's processive motion is lacking. To overcome this deficiency, we developed the first (to our knowledge) computational model for two-headed dynein that couples conformational changes of the motor's subunits to the biochemical steps involved in ATP hydrolysis. Analysis of the model provides what we believe are several novel insights into how the protein functions: 1), structural constraints limit the motion of the free microtubule binding domain to one dimension, increasing the efficiency with which this domain finds a binding site; 2), in addition to the power stroke of the bound head, recovery of the free head to a pre-power-stroke conformation is required for this head to reach a forward binding site; 3), the order in which the power stroke and recovery transitions occur affects the probability of back-stepping; and 4), the existence of multiple equilibria in the motor's bending energy provides a mechanism for processive back-stepping. To the best of our knowledge, our computational model provides the first complete mechanochemical description of the motor protein dynein, and the findings presented here should motivate new experimental investigations to test its predictions.

Original languageEnglish (US)
Pages (from-to)144-150
Number of pages7
JournalBiophysical journal
Volume101
Issue number1
DOIs
StatePublished - Jul 6 2011

All Science Journal Classification (ASJC) codes

  • Biophysics

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