Microtubules dual chemo and thermo-responsive depolymerization

Proteins
Z Li, L Alisaraie

Abstract

The effects of chemotherapeutic agent vinblastine versus low temperature of 277 K were investigated on the structure of αβ-tubulin heterodimer by means of molecular dynamics simulations. Individual experiments have shown that the vinblastine-bound heterodimer, and its apo structure under low temperature of 277 K, both undergo conformational changes toward destabilization of the dimer as compared to the apo tubulin at 300 K. Both factors exhibited weakening of the longitudinal interactions of tubulin heterodimer through displacing dimer interfacial segments, resulting in dominant electrostatic repulsion at the interface of the subunits. The two independent factors of temperature and anti-mitotic agent facilitate alteration of secondary structure in functional segments such as H1-S2 loop, H3, H10 helices, and T7 loop, which are known to be important in either longitudinal or lateral contacts among αβ-heterodimers in MTs protofilaments and their depolymerization mechanism.

References

Nov 25, 1977·Journal of Molecular Biology·K A Johnson, G G Borisy
Jan 1, 1983·Annual Review of Biophysics and Bioengineering·J J Correia, R C Williams
Jun 15, 1993·The Biochemical Journal·N C KaarsholmS I Hansen
Aug 23, 1996·Journal of Molecular Biology·M RareyG Klebe
Jan 1, 1997·Annual Review of Cell and Developmental Biology·A Desai, T J Mitchison
Jun 17, 1998·Nature Structural Biology·E NogalesJ Löwe
Aug 1, 1994·Physical Review. E, Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics·D K FygensonA Libchaber
Jan 7, 2000·Journal of Molecular Biology·H GohlkeG Klebe
Nov 9, 2001·Journal of Molecular Biology·J LöweE Nogales
Jan 30, 2002·Cellular and Molecular Life Sciences : CMLS·O ValironD Job
Jul 19, 2002·Biophysical Journal·Ozlem KeskinDavid G Covell
Apr 8, 2003·Current Medicinal Chemistry. Anti-cancer Agents·M A Jordan
Jun 26, 2003·Protein Science : a Publication of the Protein Society·María Soledad CelejGerardo D Fidelio
Feb 24, 2004·Journal of Computational Chemistry·Eran EyalVladimir Sobolev
Apr 2, 2004·Nature Reviews. Cancer·Mary Ann Jordan, Leslie Wilson
Jul 21, 2004·Journal of Computational Chemistry·Chris OostenbrinkWilfred F van Gunsteren
May 27, 2005·Nature·Benoît GigantMarcel Knossow
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen
May 23, 2008·Langmuir : the ACS Journal of Surfaces and Colloids·A KisL Forró
Jul 1, 2009·Molecular Biotechnology·Richard H Wade
Apr 8, 2010·The Journal of Biological Chemistry·Odile ValironDidier Job
Mar 8, 2011·Medicinal Research Reviews·Richard A StantonRitu Aneja
Jul 26, 2011·Chemical Biology & Drug Design·Laleh Alisaraie, Jack A Tuszynski
Aug 8, 2012·Acta Crystallographica. Section D, Biological Crystallography·Fanomezana M RanaivosonMarcel Knossow
Mar 1, 2008·Journal of Chemical Theory and Computation·Berk HessErik Lindahl

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