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Structural Features and Lipid Binding Domain of Tubulin on Biomimetic Mitochondrial Membranes

Published

Author(s)

David Paul Hoogerheide, Sergei Y. Noskov, Daniel Jacobs, Lucie Bergdoll, Vitalii Ivanovich Silin, David L. Worcester, Jeff Abramson, Hirsh Nanda, Tatiana K. Rostovtseva, Sergey M. Bezrukov

Abstract

Amphitropic proteins, the subfamily of peripheral membrane proteins that interact directly with lipid bilayers, comprises members whose function depends on their localization either in the cytosol or at the cellular membranes. Despite the well-established involvement of these "dual function" proteins in a variety of cellular processes, the exact mechanism of their interaction with cellular membranes is still not well understood. Here we show that dimeric tubulin, an abundant water-soluble cytosolic protein known primarily for its role in the cytoskeleton, exhibits weak binding to biomimetic "mitochondrial" membranes in a manner characteristic of peripheral membrane proteins and differentiates between the two zwitterionic lipids dioleoylphosphatidylethanolamine (DOPE) and dioleoylphosphatidylcholine (DOPC). Using five independent techniques - surface plasmon resonance, electrochemical impedance spectroscopy, bilayer overtone analysis, neutron reflectometry, and molecular dynamics simulations - we quantify tubulin binding and elucidate the dimer orientation on the membrane surface. Our results suggest that amphipathic α-helix H10 and a highly conserved tryptophan residue on α-tubulin are responsible for binding to membrane surfaces. A similar region on β-tubulin may also contribute. The strong enhancement of binding in DOPE-containing membranes is proposed to arise from the insertion of the binding helix into the PE headgroup region, where both hydrophobic and electrostatic interactions play a role. The identification of the tubulin dimer orientation and membrane-binding domain may be important step toward our understanding of the complex mechanism by which tubulin interacts with the voltage-dependent anion channel (VDAC) in the mitochondrial outer membrane.
Citation
Journal of the American Chemical Society
Volume
114
Issue
18

Keywords

neutron reflectometry, peripheral membrane protein, surface plasmon resonance, electrochemical impedance spectroscopy, bilayer overtone analysis, molecular dynamics simulations, tubulin, mitochondrial regulation

Citation

, D. , , S. , Jacobs, D. , Bergdoll, L. , , V. , Duewer, D. , Abramson, J. , , H. , , T. and , S. (2017), Structural Features and Lipid Binding Domain of Tubulin on Biomimetic Mitochondrial Membranes, Journal of the American Chemical Society, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=921114 (Accessed March 5, 2024)
Created April 18, 2017, Updated September 8, 2017