Mercury Ion Binding to Apolipoprotein E Variants ApoE2, ApoE3, and ApoE4: Similar Binding Affinities but Different Structure Induction Effects

Elina Berntsson; Merlin Sardis; Andra Noormägi; Jüri Jarvet; Per M Roos; Vello Tõugu; Astrid Gräslund; Peep Palumaa; Sebastian K T S Wärmländer

doi:10.1021/acsomega.2c02254

Mercury Ion Binding to Apolipoprotein E Variants ApoE2, ApoE3, and ApoE4: Similar Binding Affinities but Different Structure Induction Effects

ACS Omega. 2022 Aug 12;7(33):28924-28931. doi: 10.1021/acsomega.2c02254. eCollection 2022 Aug 23.

Authors

Elina Berntsson^{1

2}, Merlin Sardis¹, Andra Noormägi¹, Jüri Jarvet^{2

3

4}, Per M Roos^{5

6}, Vello Tõugu¹, Astrid Gräslund^{2

4}, Peep Palumaa¹, Sebastian K T S Wärmländer^{2

4}

Affiliations

¹ Department of Chemistry and Biotechnology, Tallinn University of Technology, 12618 Tallinn, Estonia.
² Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden.
³ The National Institute of Chemical Physics and Biophysics, 12618 Tallinn, Estonia.
⁴ CellPept Sweden AB, Kvarngatan 10B, 118 47 Stockholm, Sweden.
⁵ Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.
⁶ Department of Clinical Physiology, Capio Saint Göran Hospital, 112 19 Stockholm, Sweden.

Abstract

Mercury intoxication typically produces more severe outcomes in people with the APOE-ε4 gene, which codes for the ApoE4 variant of apolipoprotein E, compared to individuals with the APOE-ε2 and APOE-ε3 genes. Why the APOE-ε4 allele is a risk factor in mercury exposure remains unknown. One proposed possibility is that the ApoE protein could be involved in clearing of heavy metals, where the ApoE4 protein might perform this task worse than the ApoE2 and ApoE3 variants. Here, we used fluorescence and circular dichroism spectroscopies to characterize the in vitro interactions of the three different ApoE variants with Hg(I) and Hg(II) ions. Hg(I) ions displayed weak binding to all ApoE variants and induced virtually no structural changes. Thus, Hg(I) ions appear to have no biologically relevant interactions with the ApoE protein. Hg(II) ions displayed stronger and very similar binding affinities for all three ApoE isoforms, with K _D values of 4.6 μM for ApoE2, 4.9 μM for ApoE3, and 4.3 μM for ApoE4. Binding of Hg(II) ions also induced changes in ApoE superhelicity, that is, altered coil-coil interactions, which might modify the protein function. As these structural changes were most pronounced in the ApoE4 protein, they could be related to the APOE-ε4 gene being a risk factor in mercury toxicity.