Sequence diversity of tubulin isotypes in regulation of the mitochondrial voltage-dependent anion channel

The Journal of Biological Chemistry
Tatiana K RostovtsevaSergey M Bezrukov

Abstract

The microtubule protein tubulin is a heterodimer comprising α/β subunits, in which each subunit features multiple isotypes in vertebrates. For example, seven α-tubulin and eight β-tubulin isotypes in the human tubulin gene family vary mostly in the length and primary sequence of the disordered anionic carboxyl-terminal tails (CTTs). The biological reason for such sequence diversity remains a topic of vigorous enquiry. Here, we demonstrate that it may be a key feature of tubulin's role in regulation of the permeability of the mitochondrial outer membrane voltage-dependent anion channel (VDAC). Using recombinant yeast α/β-tubulin constructs with α-CTTs, β-CTTs, or both from various human tubulin isotypes, we probed their interactions with VDAC reconstituted into planar lipid bilayers. A comparative study of the blockage kinetics revealed that either α-CTTs or β-CTTs block the VDAC pore and that the efficiency of blockage by individual CTTs spans 2 orders of magnitude, depending on the CTT isotype. β-Tubulin constructs, notably β3, blocked VDAC most effectively. We quantitatively described these experimental results using a physical model that accounted only for the number and distribution of charges in the CTT, and not for the in...Continue Reading

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Citations

Aug 11, 2019·Experimental Biology and Medicine·Matthew A CaporizzoBenjamin L Prosser
Jan 15, 2020·The Journal of General Physiology·María Queralt-MartínTatiana K Rostovtseva
Nov 25, 2019·Cellular and Molecular Life Sciences : CMLS·Amandine RoviniTatiana K Rostovtseva
Feb 28, 2019·American Journal of Physiology. Cell Physiology·Kati MadoTuuli Kaambre
Jan 23, 2021·International Journal of Molecular Sciences·Paulina SanderJohann Schredelseker
Apr 28, 2020·Biochemical Pharmacology·Raymond J Winquist, Valentin K Gribkoff
May 11, 2021·Biochimica Et Biophysica Acta. Biomembranes·David P HoogerheideSergey M Bezrukov
Jul 25, 2021·International Journal of Molecular Sciences·Tatiana K RostovtsevaDavid P Hoogerheide
Sep 11, 2021·ACS Chemical Neuroscience·Altmash KhanRadhakrishnan Mahalakshmi

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