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Mol Biol Cell. 2019 Nov 15;30(24):2953-2968. doi: 10.1091/mbc.E19-05-0247. Epub 2019 Oct 10.

Multivalent electrostatic microtubule interactions of synthetic peptides are sufficient to mimic advanced MAP-like behavior.

Author information

1
B CUBE-Center for Molecular Bioengineering, Technische -Universität -Dresden, Dresden 01307, Germany.
2
Cluster of Excellence Physics of Life, Technische -Universität -Dresden, Dresden 01307, Germany.
3
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden 01307, Germany.

Abstract

Microtubule-associated proteins (MAPs) are a functionally highly diverse class of proteins that help to adjust the shape and function of the microtubule cytoskeleton in space and time. For this purpose, MAPs structurally support microtubules, modulate their dynamic instability, or regulate the activity of associated molecular motors. The microtubule-binding domains of MAPs are structurally divergent, but often depend on electrostatic interactions with the negatively charged surface of the microtubule. This suggests that the surface exposure of positive charges rather than a certain structural fold is sufficient for a protein to associate with microtubules. Consistently, positively charged artificial objects have been shown to associate with microtubules and to diffuse along their lattice. Natural MAPs, however, show a more sophisticated functionality beyond lattice-diffusion. Here, we asked whether basic electrostatic interactions are sufficient to also support advanced MAP functionality. To test this hypothesis, we studied simple positively charged peptide sequences for the occurrence of typical MAP-like behavior. We found that a multivalent peptide construct featuring four lysine-alanine heptarepeats (starPEG-(KA7)4)-but not its monovalent KA7-subunits-show advanced, biologically relevant MAP-like behavior: starPEG-(KA7)4 binds microtubules in the low nanomolar range, diffuses along their lattice with the ability to switch between intersecting microtubules, and tracks depolymerizing microtubule ends. Further, starPEG-(KA7)4 promotes microtubule nucleation and growth, mediates depolymerization coupled pulling at plus ends, and bundles microtubules without significantly interfering with other proteins on the microtubule lattice (as exemplified by the motor kinesin-1). Our results show that positive charges and multivalency are sufficient to mimic advanced MAP-like behavior.

PMID:
31599700
DOI:
10.1091/mbc.E19-05-0247

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