Correlation of Genomic Mutations with Functionality and Structural Changes Resulting in Proteins Associated With Autoimmune Diseases with Molecular Dynamics Methods

Postgraduate Thesis uoadl:2711395 493 Read counter

Unit:
Κατεύθυνση Βιοπληροφορική
Library of the School of Science
Deposit date:
2018-03-20
Year:
2018
Author:
Lesgidou Nastazia-Lemonia
Supervisors info:
Ηλίας Ηλιόπουλος, Καθηγητής, Τμήμα Βιοτεχνολογίας, Γεωπονικό Πανεπιστήμιου Αθηνών
Μεταξία Βλάσση, Ερευνήτρια Α, Ινστιτούτου Βιοεπιστημών και Εφαρμογών, Ε.Κ.Ε.Φ.Ε Δημόκριτος
Original Title:
Συσχέτιση Γονιδιακών Μεταλλάξεων με την Λειτουργικότητα και τις Δομικές Αλλαγές που Προκύπτουν σε Πρωτεΐνες που Σχετίζονται με Αυτοάνοσα Νοσήματα με Μεθόδους Μοριακής Δυναμικής
Languages:
Greek
Translated title:
Correlation of Genomic Mutations with Functionality and Structural Changes Resulting in Proteins Associated With Autoimmune Diseases with Molecular Dynamics Methods
Summary:
TYK2 is an ATP-dependent tyrosine kinase that belongs to the Janus Kinase family (JAKS) and it is found to play a very important role in the signaling pathway I IFN. The structure of TYK2 can be divided into two independent regions, the N-terminal lobe (residues: 889-979) and the C-terminal lobe (residues: 985-1176). The activation loop (residues 1047-1060) is located at the start of the C-terminal lobe, containing two sequential Tyrosines (Y1054, Y1055) that can be phosphorylated and have been found to play an important role in the activation of TYK2.
In many recent clinical studies and meta-analyses it is reported that a particular SNP (rs34536443), generated when Proline 1104 mutates to alanine (P1104A), affects the catalytic activity of TYK2 and acts as a protective variant to autoimmune diseases such as systemic lupus, rheumatoid arthritis, endometriosis and infertility, and multiple sclerosis. In order to investigate the structural consequences and the
structure/function relationships accompanying the Pro1104 to Ala mutation, we combined 3D-modeling and MD simulations of this TYK2 variant and of the wild-type TYK2, for comparison (in all the APO- ADP- and ATP-bound forms).
Main subject category:
Science
Keywords:
TYK2, Molecular Dynamics, JAK kinase, Autoimmune disseases, mutation, P1104A
Index:
Yes
Number of index pages:
16
Contains images:
Yes
Number of references:
30
Number of pages:
85
Thesis_final_Nastazia_Lesgidou.pdf (29 MB) Open in new window