6533b828fe1ef96bd128905a

RESEARCH PRODUCT

Copper(II)-Induced Restructuring of ZnuD, a Zinc(II) Transporter from Neisseria meningitidis.

Magdalena Rowinska-zyrekHenryk KozłowskiAleksandra Hecel

subject

Models MolecularConformational changeMetal ions in aqueous solutionchemistry.chemical_elementZincNeisseria meningitidis010402 general chemistry01 natural sciencesInorganic ChemistryBacterial ProteinsHumansProlineAmino Acid SequencePhysical and Theoretical ChemistryCation Transport ProteinsPolyproline helix010405 organic chemistryTransporterCopper0104 chemical sciencesMeningococcal InfectionsCrystallographyZincchemistryHelixThermodynamicsCopperProtein Binding

description

Cluster 2 (288HDDDNAHAHTH298) from Neisseria meningitidis ZnuD is a flexible loop that captures zinc(II) ions, acting as a "fishing net". We describe its Zn(II) and Cu(II) binding capabilities, focusing on the thermodynamics of such interactions and comparing them with the complexes of the 1MAHHHHHHL9-NH2 region. Copper(II) complexes with the studied ZnuD regions are thermodynamically more stable than the zinc(II) ones-Cu(II) complexes dominate in solution even in close to physiological ratios of the studied metal ions (a 10-fold excess of Zn(II) over Cu(II)). While the binding of native Zn(II) has no significant impact on the structure of its transporter, Cu(II) binding induces a conformational change of cluster 2 to a polyproline II-like helix. To the best of our knowledge, this is the first evidence of a copper(II)-induced formation of a polyproline II-like structure in a sequence that does not contain proline residues. Cu(II) coordination also changes the structure of an intracellular, N-terminal, His-rich region, folding it to an α helix.

10.1021/acs.inorgchem.9b00265https://pubmed.ncbi.nlm.nih.gov/30986048