Structural evidence for cooperative microtubule stabilization by taxol and the endogenous dynamics regulator MAP4

Hui Xiao, Hui Wang, Xuechun Zhang, Zongcai Tu, Chloë Bulinski, Marina Khrapunovich-Baine, Ruth Hogue Angeletti, Susan Band Horwitz

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Microtubules (MTs) composed of αβ-tubulin heterodimers are highly dynamic polymers, whose stability can be regulated by numerous endogenous and exogenous factors. Both the antimitotic drug Taxol and microtubule- associated proteins (MAPs) stabilize this dynamicity by binding to and altering the conformation of MTs. In the current study, amide hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) was used to examine the structural and dynamic properties of the MT complex with the microtubule binding domain of MAP4 (MTB-MAP4) in the presence and absence of Taxol. The changes in the HDX levels indicate that MTB-MAP4 may bind to both the outside and the luminal surfaces of the MTs and that Taxol reduces both of these interactions. The MTB-MAP4 binding induces conformational rearrangements of α- and β-tubulin that promote an overall stabilization of MTs. Paradoxically, despite Taxol's negative effects on MAP4 interactions with the MTs, its binding to the MTB-MAP4-MT complex further reduces the overall deuterium incorporation, suggesting that a more stable complex is formed in the presence of the drug.

Original languageEnglish (US)
Pages (from-to)744-752
Number of pages9
JournalACS Chemical Biology
Volume7
Issue number4
DOIs
StatePublished - Apr 20 2012

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Paclitaxel
Microtubules
Stabilization
Deuterium
Tubulin
Antimitotic Agents
Microtubule-Associated Proteins
Amides
Mass spectrometry
Conformations
Hydrogen
Polymers
MAP4
Pharmaceutical Preparations
Mass Spectrometry

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Structural evidence for cooperative microtubule stabilization by taxol and the endogenous dynamics regulator MAP4. / Xiao, Hui; Wang, Hui; Zhang, Xuechun; Tu, Zongcai; Bulinski, Chloë; Khrapunovich-Baine, Marina; Hogue Angeletti, Ruth; Band Horwitz, Susan.

In: ACS Chemical Biology, Vol. 7, No. 4, 20.04.2012, p. 744-752.

Research output: Contribution to journalArticle

Xiao, H, Wang, H, Zhang, X, Tu, Z, Bulinski, C, Khrapunovich-Baine, M, Hogue Angeletti, R & Band Horwitz, S 2012, 'Structural evidence for cooperative microtubule stabilization by taxol and the endogenous dynamics regulator MAP4', ACS Chemical Biology, vol. 7, no. 4, pp. 744-752. https://doi.org/10.1021/cb200403x
Xiao, Hui ; Wang, Hui ; Zhang, Xuechun ; Tu, Zongcai ; Bulinski, Chloë ; Khrapunovich-Baine, Marina ; Hogue Angeletti, Ruth ; Band Horwitz, Susan. / Structural evidence for cooperative microtubule stabilization by taxol and the endogenous dynamics regulator MAP4. In: ACS Chemical Biology. 2012 ; Vol. 7, No. 4. pp. 744-752.
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