Structural characterization of the intrinsically disordered domain of Mycobacterium tuberculosis protein tyrosine kinase A

  • Although intrinsically disordered proteins or protein domains (IDPs or IDD) are less abundant in bacteria than in eukaryotes, their presence in pathogenic bacterial proteins is important for protein-protein interactions. The protein tyrosine kinase A (PtkA) from Mycobacterium tuberculosis possesses an 80-residue disordered region (IDDPtkA ) of unknown function, located N-terminally to the well-folded kinase core domain. Here, we characterize the conformation of IDDPtkA under varying biophysical conditions and phosphorylation using NMR-spectroscopy. Our results confirm that the N-terminal domain of PtkA exists as an IDD at physiological pH. Furthermore, phosphorylation of IDDPtkA increases the activity of PtkA. Our findings will complement future approaches in understanding molecular mechanisms of key proteins in pathogenic virulence.

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Author:Anna Niesteruk, Marie Hutchison, Sridhar Sreeramulu, Hendrik R. A. Jonker, Christian RichterORCiD, Rupert Abele, Christoph Bock, Harald SchwalbeORCiDGND
Pubmed Id:
Document Type:Article
Year of Completion:2019
Date of first Publication:2018/03/01
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/09/25
Tag:Mycobacterium tuberculosis; intrinsically disordered protein; nuclear magnetic resonance spectroscopy; protein denaturation; protein phosphorylation; protein tyrosine kinase
Page Number:13
First Page:1233
Last Page:1245
Postprint, zuerst in: FEBS Letters, 592.2018, 7, S. 1233-1245. doi: 10.1002/1873-3468.13022, doi:10.1002/1873-3468.13022
Gefördert durch: European Union: Horizon 2020. Infrastructure for NMR, EM and X-rays for Translational Research, iNEXT, H2020 Grant # 653706
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoDeutsches Urheberrecht