Effect of Nucleotide State on the Protofilament Conformation of Tubulin Octamers

The Journal of Physical Chemistry. B
Anjela ManandharSharon M Loverde

Abstract

At the molecular level, the dynamic instability (random growth and shrinkage) of the microtubule (MT) is driven by the nucleotide state (GTP vs GDP) in the β subunit of the tubulin dimers at the MT cap. Here, we use large-scale molecular dynamics (MD) simulations and normal-mode analysis (NMA) to characterize the effect of a single GTP cap layer on tubulin octamers composed of two neighboring protofilaments (PFs). We utilize recently reported high-resolution structures of dynamic MTs to simulate a GDP octamer both with and without a single GTP cap layer. We perform multiple replicas of long-time atomistic MD simulations (3 replicas, 0.3 μs for each replica, 0.9 μs for each octamer system, and 1.8 μs total) of both octamers. We observe that a single GTP cap layer induces structural differences in neighboring PFs, finding that one PF possesses a gradual curvature, compared to the second PF which possesses a kinked conformation. This results in either curling or splaying between these PFs. We suggest that this is due to asymmetric strengths of longitudinal contacts between the two PFs. Furthermore, using NMA, we calculate mechanical properties of these octamer systems and find that octamer system with a single GTP cap layer posses...Continue Reading

References

Feb 22, 1979·Nature·P B SchiffS B Horwitz
Jan 1, 1978·The Journal of Cell Biology·G B PiersonR H Himes
Sep 1, 1991·The Journal of Cell Biology·E M MandelkowR A Milligan
Jan 1, 1991·Biology of the Cell·D Chrétien, R H Wade
Feb 5, 1985·Journal of Molecular Biology·M LevittP S Stern
Feb 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·Y D Chen, T L Hill
Nov 15, 1984·Nature·T Mitchison, M Kirschner
Dec 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·Y Chen, T L Hill
Aug 1, 1995·The Journal of Cell Biology·B Mickey, J Howard
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Jan 1, 1997·Cell Motility and the Cytoskeleton·E T O'BrienH P Erickson
Jan 1, 1997·Annual Review of Cell and Developmental Biology·A Desai, T J Mitchison
May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·T Müller-ReichertA A Hyman
Feb 13, 2001·Biophysical Journal·A R AtilganI Bahar
Nov 9, 2001·Journal of Molecular Biology·J LöweE Nogales
Dec 12, 2001·Molecular Biology of the Cell·K R Anders, D Botstein
Jul 19, 2002·Biophysical Journal·Ozlem KeskinDavid G Covell
Dec 31, 2003·Methods in Enzymology·András Fiser, Andrej Sali
Mar 9, 2004·Journal of Molecular Biology·Jennifer H ShinPaul Matsudaira
Sep 30, 2004·Biophysical Journal·Marcel E Janson, Marileen Dogterom
Feb 26, 2005·EMBO Reports·Angelika KrebsAndreas Hoenger
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Dec 13, 2005·Biophysical Journal·Mahito KikumotoHideo Tashiro
Jun 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Francesco PampaloniErnst-Ludwig Florin
Mar 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·M G L Van den HeuvelC Dekker
Jul 1, 2009·Molecular Biotechnology·Richard H Wade
Aug 13, 2009·The Journal of Physical Chemistry. B·Joost van MamerenChristoph F Schmidt
Sep 30, 2009·Chemical Reviews·Ivet BaharIndira H Shrivastava
Dec 24, 2009·The Journal of Physical Chemistry. B·Laura RiccardiGerhard Stock
Apr 7, 2010·Physical Review Letters·David Sept, Fred C MacKintosh
Oct 7, 2010·Biophysical Journal·Marco A DeriuAlberto Redaelli
Mar 15, 2011·Structure·Andrea Grafmüller, Gregory A Voth
Apr 8, 2011·Bioinformatics·Ahmet BakanIvet Bahar
Apr 19, 2011·Journal of Computational Chemistry·Naveen Michaud-AgrawalOliver Beckstein
Nov 9, 2011·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Xiang-Ying Ji, Xi-Qiao Feng

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Citations

Feb 5, 2021·Annals of Biomedical Engineering·Mahya Hemmat, David J Odde
Jul 4, 2021·European Biophysics Journal : EBJ·Alexandr NasedkinJan Swenson

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