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Volume 10, Issue 8 (Suppl)
J Proteomics Bioinform, an open access journal
ISSN: 0974-276X
Structural Biology 2017
September 18-20, 2017
9
th
International Conference on
Structural Biology
September 18-20, 2017 Zurich, Switzerland
An atomistic view of microtubule stabilization by GTP
Liliane Mouawad
Institut Curie, France
A
microtubule is a dynamic system formed of
α
β-tubulins. The presence of nonhydrolyzable guanosine-5’-triphosphate
(GTP)/guanosine diphosphate (GDP) on the β-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
γ
-phosphate of GTP. Sequence
alignments of several tubulins confirm the importance of these residues.
Biography
Liliane Mouawad was always interested in understanding the mechanism of action of proteins or protein assemblies. This understanding may be based on either
molecular simulations or on experiments like NMR. But her expertise is primarily in molecular dynamics simulations and more precisely in normal mode analysis
(NMA). She has developed several methods going from the calculation of normal modes of very large systems or of images, to the calculation of the pathway
between two protein conformations, to the prediction of the compactness of a calcium-binding protein. Recently she was also involved in docking and virtual
screening themes, where she has acquired enough expertise to develop a new consensus methodology to overcome some issues observed in these approaches.
liliane.mouawad@curie.frLiliane Mouawad, J Proteomics Bioinform 2017, 10:8(Suppl)
DOI: 10.4172/0974-276X-C1-0100