Characterization of the PATZ1 BTB domain

Piepoli, Sofia (2020) Characterization of the PATZ1 BTB domain. [Thesis]

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The BTB domain is a conserved, multi-functional protein interaction domain engaged in the coordination of various large protein complexes, including ion channels, degradation signaling complexes and DNA transcription factors. The ZBTB protein family of transcription regulators is characterized by an N-terminal BTB domain followed by a variable number of Zinc Fingers and it is involved in cellular proliferation, immune cell lineage differentiation, and cancer development. Among the 49 human ZBTB proteins, PATZ1 stands out with a unique extra 31-amino acids long sequence in the center of the BTB domain. The central loop of PATZ1 is an intrinsically disordered region (IDR) conserved in mammals but absent in fish and has high binding potential. PATZ1 is a ubiquitous transcription factor that plays a role in numerous cancer types and interferes with the p53 tumor suppressor. In this thesis work, the determination of the unique structural features of the PATZ1 BTB domain was primarily accomplished with the solution of its crystal structure as a homodimer in both mouse and zebrafish (PDB IDs: 6GUV and 6GUW). Although similar in the 3D fold and the dimerization interface to the BCL6 BTB domain, the new crystal structures suggest that the PATZ1 co-repressors binding site contains a divergent sequence. The molecular dynamics of the new protein structures compared to other previously known structures allowed us to classify ZBTBs family members. Finally, the formation of stable BTB heterodimers with selected ZBTB proteins was computationally demonstrated
Item Type: Thesis
Uncontrolled Keywords: BTB domain, PATZ1 transcription factor. -- Protein Crystallization. -- Dimerization, Molecular Dynamics. -- BTB alanı. -- PATZ1 transkripsiyon faktörü. -- Protein kristalizasyon. -- Dimerizasyon. -- Moleküler Dinamikler.
Subjects: T Technology > TA Engineering (General). Civil engineering (General) > TA164 Bioengineering
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: IC-Cataloging
Date Deposited: 25 Oct 2020 21:14
Last Modified: 26 Apr 2022 10:34

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