Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Aug 19:6:31723.
doi: 10.1038/srep31723.

Maintenance of electrostatic stabilization in altered tubulin lateral contacts may facilitate formation of helical filaments in foraminifera

David M Bassen  1 , Yubo Hou  2 , Samuel S Bowser  2   3 , Nilesh K Banavali  1   4
Affiliations

Maintenance of electrostatic stabilization in altered tubulin lateral contacts may facilitate formation of helical filaments in foraminifera

David M Bassen et al. Sci Rep. .

Abstract

Microtubules in foraminiferan protists (forams) can convert into helical filament structures, in which longitudinal intraprotofilament interactions between tubulin heterodimers are thought to be lost, while lateral contacts across protofilaments are still maintained. The coarse geometric features of helical filaments are known through low-resolution negative stain electron microscopy (EM). In this study, geometric restraints derived from these experimental data were used to generate an average atomic-scale helical filament model, which anticipated a modest reorientation in the lateral tubulin heterodimer interface. Restrained molecular dynamics (MD) simulations of the nearest neighbor interactions combined with a Genalized Born implicit solvent model were used to assess the lateral, longitudinal, and seam contacts in 13-3 microtubules and the reoriented lateral contacts in the helical filament model. This electrostatic analysis suggests that the change in the lateral interface in the helical filament does not greatly diminish the lateral electrostatic interaction. After longitudinal dissociation, the 13-3 seam interaction is much weaker than the reoriented lateral interface in the helical filament model, providing a plausible atomic-detail explanation for seam-to-lateral contact transition that enables the transition to a helical filament structure.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Modeling the helical filament state with a single particle representation of each tubulin monomer.
(A) Detailed αβ-tubulin heterodimer structure, (B) Coarse grained model where every monomer is represented by a single point mass, (C) 13-3 architecture in this coarse-grained model, (D) Average helical filament architecture in this coarse-grained model.
Figure 2
Figure 2. A workflow to predict an atomic-detail foram helical filament model.
(A) Average coarse-grained helical filament model predicted using negative stain EM data; (B) Each tubulin heterodimer represented by two center-of-mass points; (C) Overlay of axially oriented foram tubulin monomer homology models on their corresponding center-of-mass; (D) Extraction of 10 reference C-α atoms from overlaid foram tubulin heterodimer homology model; (E) Cylindrical restraints reorient 10 reference C-α atoms with respect to central helical filament axis through rotation around individual heterodimer axis; (F) Overlay foram tubulin heterodimer homology model on 10 reference reoriented C-α atoms; (G) Atomic-detail helical filament model built using steps (B–F) for each coarse-grained foram tubulin heterodimer.
Figure 3
Figure 3. A comparison of top and side views indicating subtle differences between lateral interactions in a 13-3 microtubule and the average helical filament model.
Figure 4
Figure 4. Foram tubulin inter-dimer interfaces and their electrostatic interaction energy distributions.
(A) Four foram tubulin inter-dimer nearest-neighbor interfaces evaluated, (B) Overall electrostatic interaction energy distributions for the four interfaces, (C) Coulombic inter-dimer interaction energy distributions for the four interfaces, (D) Solvation electrostatic inter-dimer interaction energy distributions for the four interfaces. Interaction energies from all 5 simulations for each tetramer were pooled together, and the probability distributions were generated as histograms with a bin width of either 1 kcal/mol or 10 kcal/mol.
Figure 5
Figure 5. Tubulin assembly structures consisting of 50 tubulin heterodimers to illustrate structural changes required to form helical filaments consistent with the negative stain EM data.
(A,B) 13-3 microtubule assembly, (C,D) helical filament with 13-3 lateral interface maintained, but not compliant with the geometric parameter range of the negative stain EM data, (E,F) helical filament representing the average of the geometric parameter range of the negative stain EM data, but with lateral interface changed as compared to 13-3 architecture. Tubulin dimers 1–13 are shown in red, tubulin dimers 14–26 are shown in green, tubulin dimers 27–39 are shown in cyan, and the rest of the tubulin dimers are shown in blue.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Avila J. Microtubule functions. Life Sciences 50, 327–334 (1992). - PubMed
    1. Tsutsui H. et al.. Role of microtubules in contractile dysfunction of hypertrophied cardiocytes. Circulation 90, 533–555 (1994). - PubMed
    1. Kosik K., Joachim C. & Selkoe D. Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease. Proceedings of the National Academy of Sciences USA 83, 4044–4048 (1986). - PMC - PubMed
    1. Zhou J. & Giannakakou P. Targeting microtubules for cancer chemotherapy. Current Medicinal Chemistry - Anti-Cancer Agents 5, 65–71 (2005). - PubMed
    1. Nogales E., Wolf S. & Downing K. Structure of the αβ-tubulin dimer by electron crystallography. Nature 199–202 (1998). - PubMed

Publication types

LinkOut - more resources