NDLI: Probing the origin of tubulin rigidity with molecular simulations

Content Provider	PubMed Central
Author	Dima, Ruxandra I. Joshi, Harshad
Abstract	Tubulin heterodimers are the building blocks of microtubules, a major component of the cytoskeleton, whose mechanical properties are fundamental for the life of the cell. We uncover the microscopic origins of the mechanical response in microtubules by probing features of the energy landscape of the tubulin monomers and tubulin heterodimer. To elucidate the structures of the unfolding pathways and reveal the multiple unfolding routes, we performed simulations of a self-organized polymer (SOP) model of tubulin. The SOP representation, which is a coarse-grained description of chains, allows us to perform force-induced simulations at loading rates and time scales that closely match those used in single-molecule experiments. We show that the forced unfolding of each monomer involves a bifurcation in the pathways to the stretched state. After the unfolding of the C-term domain, the unraveling continues either from the N-term domain or from the middle domain, depending on the monomer and the pathway. In contrast to the unfolding complexity of the monomers, the dimer unfolds according to only one route corresponding to the unraveling of the C-term domain and part of the middle domain of β-tubulin. We find that this surprising behavior is due to the viscoelastic properties of the interface between the monomers. We map precise features of the complex energy landscape of tubulin by surveying the structures of the various metastable intermediates, which, in the dimer case, are characterized only by changes in the β-tubulin monomer.
Related Links	http://dx.doi.org/10.1073/pnas.0806113105
Starting Page	15743
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	41
Volume Number	105
Language	English
Publisher	National Academy of Sciences
Publisher Date	2008-10-14
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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