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Computational Investigation of Ska Complex-Tubulin Molecular Interactions to Shed Light on Force Generation Mechanisms in Kinetochore-Microtubule Junctions

Hedyeh Khoshkhoo Gilvaei

Computational Investigation of Ska Complex-Tubulin Molecular Interactions to Shed Light on Force Generation Mechanisms in Kinetochore-Microtubule Junctions.

Rel. Jacek Adam Tuszynski, Marco Agostino Deriu. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Biomedica, 2019

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Abstract:

Microtubules (MTs) are involved in several cellular processes and play a key role during mitosis, forming the mitotic spindle which is able to divide the chromosomes. The connection between microtubules and chromosomes is guaranteed by a macro structure including various motor proteins, called kinetochore. Microtubule instability, characterized by lengthening and shortening of the MTs, generates forces at the kinetochore, that lead the chromosomes toward the metaphase plate. Therefore, the stability of the junctions between kinetochore and plus end of the microtubule is a critical issue for an accurate chromosome segregation. The stability of the kinetochore-microtubule interaction is guaranteed by a W-shaped homodimer of coiled coils, called ska complex, which is crucial for a correct cell division in human cells: the MT-binding domains (MTBDs) of the ska complex recognizes tubulin monomers making transversal bindings. However, molecular mechanisms at the basis of the interaction between tubulin and ska complex is not completely understood yet. In this research, computational molecular docking has been employed to determine most likely three-dimensional configurations of ska complex docked to αβ tubulin heterodimer. Moreover, molecular phenomena induced by Ska1-MT Binding Domain (experimentally known) interaction have been deeply investigated by molecular modelling techniques with atomic resolution. In particular, classical and steered Molecular Dynamics were employed to highlight the most favorable protein-protein complex configuration and to investigate the force generation mechanism in the kinetochore-microtubule junctions. Future studies might consider binding interactions between ska complex and ring protofilaments or an entire piece of microtubule wall to shed light on force generation mechanisms driving the whole segregation process of chromosomes in human cell.

Relators: Jacek Adam Tuszynski, Marco Agostino Deriu
Academic year: 2018/19
Publication type: Electronic
Number of Pages: 71
Subjects:
Corso di laurea: Corso di laurea magistrale in Ingegneria Biomedica
Classe di laurea: New organization > Master science > LM-21 - BIOMEDICAL ENGINEERING
Aziende collaboratrici: UNSPECIFIED
URI: http://webthesis.biblio.polito.it/id/eprint/11377
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