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Liliane Mouawad

Liliane Mouawad

Institut Curie, France

Title: An Atomistic View of Microtubule Stabilization by GTP

Biography

Biography: Liliane Mouawad

Abstract

A microtubule is a dynamic system formed of ab-tubulins. The presence of nonhydrolyzable guanosine-5’-triphosphate (GTP)/guanosine diphosphate (GDP) on the b-tubulins provokes microtubule polymerization/depolymerization. Despite the large number of experimental studies of this dynamical process, its mechanism is still unclear. To provide insights into this mechanism, we studied the first depolymerization steps of GDP/GTP-bound microtubules by normal-mode analysis with the all-atom model. We also constructed a depolymerizing microtubule and compared it to cryo-electron microscopy tomograms (cyro-ET). The results show that during depolymerization, the protofilaments not only curve but twist to weaken their lateral interactions. These interactions are stabilized by GTP, but not evenly. Not all of the interface residues are of equal importance: five of them, belonging to the H2-S3 loop, play a special role; acting as a lock whose key is the g-phosphate of GTP. Sequence alignments of several tubulins confirm the importance of these residues.

References:

  1. Chaput L, Martinez‑Sanz J, Saettel N, Mouawad L (2016) Benchmark of four popular virtual screening programs: construction of the active/decoy dataset remains a major determinant of measured performance. J Cheminform 8:56-72.
  2. Chaput L, Martinez‑Sanz J, Quiniou E, Rigolet P, Saettel N, Mouawad L (2016) vSDC: a method to improve early recognition in virtual screening when limited experimental resources are available. J Cheminform 8:1-18.
  3. Quiniou E, Guichard P, Perahia D, Marco S, Mouawad L (2013) An atomistic view of microtubule stabilization by GTP Structure 21: 833–843.
  4. Martinez-Sanz J, Kateb F, Assairi L, Blouquit Y, Bodenhausen G, Abergel D, Mouawad L, Craescu CT (2010) Structure, dynamics and thermodynamics of the human centrin 2/hSfi1 complex. J. Mol. Biol. 395: 191–204.
  5. Mouawad L, Isvoran A, Quiniou E, Craescu CT (2009) What determines the degree of compactness of a calcium-binding protein? FEBS Journal 276:1082–1093.