Histidine-Rich C-Terminal Tail of Mycobacterial GroEL1 and Its Copper Complex-The Impact of Point Mutations
Rola, Anna (University of Wroclaw)
Palacios Bonilla, Òscar (Universitat Autònoma de Barcelona. Departament de Química)
Capdevila Vidal, Mercè (Universitat Autònoma de Barcelona. Departament de Química)
Valensin, Daniela (University of Siena)
Gumienna-Kontecka, Elżbieta (University of Wroclaw)
Potocki, Sławomir (University of Wroclaw)

Data:	2023
Resum:	The mycobacterial histidine-rich GroEL1 protein differs significantly compared to the well-known methionine/glycine-rich GroEL chaperonin. It was predicted that mycobacterial GroEL1 can play a significant role in the metal homeostasis of Mycobacteria but not, as its analogue, in protein folding. In this paper, we present the properties of the GroEL1 His-rich C-terminus as a ligand for Cu(II) ions. We studied the stoichiometry, stability, and spectroscopic features of copper complexes of the eight model peptides: L1-Ac-DHDHHHGHAH, L2-Ac-DKPAKAEDHDHHHGHAH, and six mutants of L2 in the pH range of 2-11. We revealed the impact of adjacent residues to the His-rich fragment on the complex stability: the presence of Lys and Asp residues significantly increases the stability of the system. The impact of His mutations was also examined: surprisingly, the exchange of each single His to the Gln residue did not disrupt the ability of the ligand to provide three binding sites for Cu(II) ions. Despite the most possible preference of the Cu(II) ion for the His9-His13 residues (Ac-DKPAKAED H D HHH-) of the model peptide, especially the His11 residue, the study shows that there is not only one possible binding mode for Cu(II). The significance of this phenomenon is very important for the GroEL1 function-if the single mutation occurs naturally, the protein would be still able to interact with the metal ion. The histidine-rich C-terminus (HRCT) of mycobacterial GroEL1 seems to be involved in Cu(II) homeostasis. We studied the coordination properties of model peptides: Ac-DKPAKAEDHDHHHGHAH and its six mutants in which one His residue is replaced with a Gln residue. The His9−His13 fragment has the highest affinity for Cu(II), and most probably, His11 is the main binding site for the metal ion. Interestingly, His residue rearrangement also impacts the formation of binuclear species.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Inorganic chemistry, Vol. 62, Num. 18 (April 2023) , p. 6893-6908, ISSN 1520-510X

DOI: 10.1021/acs.inorgchem.2c04486
PMID: 37092705

16 p, 3.0 MB

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