Mechanical properties of tubulin intra- And inter-dimer interfaces and their implications for microtubule dynamic instability

Thirteen tubulin protofilaments, made of αβ-tubulin heterodimers, interact laterally to produce cytoskeletal microtubules. Microtubules exhibit the striking property of dynamic instability, manifested in their intermittent growth and shrinkage at both ends. This behavior is key to many cellular processes, such as cell division, migration, maintenance of cell shape, etc. Although assembly and disassembly of microtubules is known to be linked to hydrolysis of a guanosine triphosphate molecule in the pocket of β-tubulin, detailed mechanistic understanding of corresponding conformational changes is still lacking. Here we take advantage of the recent generation of in-microtubule structures of tubulin to examine the properties of protofilaments, which serve as important microtubule assembly and disassembly intermediates. We find that initially straight tubulin protofilaments, relax to similar non-radially curved and slightly twisted conformations. Our analysis further suggests that guanosine triphosphate hydrolysis primarily affects the flexibility and conformation of the inter-dimer interface, without a strong impact on the shape or flexibility of αβ-heterodimer. Inter-dimer interfaces are significantly more flexible compared to intra-dimer interfaces. We argue that such a difference in flexibility could be key for distinct stability of the plus and minus microtubule ends. The higher flexibility of the inter-dimer interface may have implications for development of pulling force by curving tubulin protofilaments during microtubule disassembly, a process of major importance for chromosome motions in mitosis. © 2019 Fedorov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Fedorov V.A.1 , Orekhov P.S.1, 2, 3 , Kholina E.G.1 , Zhmurov A.A.2, 3 , Ataullakhanov F.I.2, 4, 5 , Kovalenko I.B. 1, 3, 6, 7, 8 , Gudimchuk N.B.4, 5
Public Library of Science
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  • 1 Department of Biology, Lomonosov Moscow State University, Moscow, Russian Federation
  • 2 Moscow Institute of Physics and Technology, Dolgoprudny, Russian Federation
  • 3 Sechenov University, Moscow, Russian Federation
  • 4 Department of Physics, Lomonosov Moscow State University, Moscow, Russian Federation
  • 5 Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russian Federation
  • 6 Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies, Federal Medical and Biological Agency of Russia, Moscow, Russian Federation
  • 7 Astrakhan State University, Astrakhan, Russian Federation
  • 8 Peoples’ Friendship University of Russia (RUDN University), Moscow, Russian Federation
Ключевые слова
dimer; guanosine triphosphate; tubulin; Article; conformational transition; controlled study; microtubule; microtubule assembly; mitosis; molecular dynamics; oligomerization; protein conformation; protein function; protein hydrolysis; protein stability; quantitative analysis
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