Monika Stachura: PAC experiments from CERN - TRI L19C and HAH1 – Niels Bohr Institute - University of Copenhagen

Monika Stachura: PAC experiments from CERN - TRI L19C and HAH1

HAH1 is a metallochaperone protein implicated in copper delivery to
the Menkes and Wilson disease proteins. In Wilson disease toxic
amounts of copper accumulate in the liver and brain, resulting in
cirrhosis and neuronal degeneration, while in Menkes syndrome the
cells' ability to absorb copper markedly decreases. Although a
substantial amount of structural data exist for HAH1, the mechanism of
copper transfer between HAH1 and Menkens and Wilson disease proteins
as well as the copper coordination geometry on metal-binding site are
still not clear enough.

The TRI L19C is a member of de novo-designed peptides family which
have the amino acid sequence G(LKALEEK)4G and which are able to
self-assemble in aqueous solution to form two and three-stranded
α-helical coiled coil. The TRI peptides are good samples to study
metalloprotein structure and folding as well as the termodynamics and
kinetiks of metal binding.

In this current study on HAH1 protein and L19C peptide, TDPAC
Spectroscopy has been used and the metal ions coordination geometries,
in the presence of Hg(II), have been determined. Received PAC spectra
show that both, TRI L19C and HAH1, reveal different metal-binding
coordination geometries, which depend on temperature and pH. pH < 8
favors formation of a linear structure, while at higher pH second
structure, with higher coordination geometry, appears. The same
tendency is observed when the temperature is raised.
 Taken together, received data provide decent information about metal-ion coordination geometries and they also support structures observed in NMR Spectroscopy.