No abstract

Of all divalent metals, mercury (Hg II ) has the highest affinity for metallothioneins. Hg II is considered to be enclosed in the α and β domains as tetrahedral α‐type Hg 4 Cys 11‐12 and β‐type Hg 3 Cys 9 clusters similar to Cd II and Zn II . However, neither the four‐fold coordination of Hg nor the existence of Hg–Hg atomic pairs have ever been demonstrated, and the Hg II partitioning among the two protein domains is unknown. Using high energy‐resolution XANES spectroscopy, MP2 geometry optimization, and biochemical analysis, evidence for the coexistence of two‐coordinate Hg‐thiolate complex and four‐coordinate Hg‐thiolate cluster with a metacinnabar‐type (β‐HgS) structure in the α domain of separate metallothionein molecules from blue mussel under in vivo exposure is provided. The findings suggest that the CXXC claw setting of thiolate donors, which only exists in the α domain, acts as a nucleation center for the polynuclear complex and that the five CXC motifs from this domain serve as the cluster‐forming motifs. Oligomerization is driven by metallophilic Hg⋅⋅⋅Hg interactions. Our results provide clues as to why Hg has higher affinity for the α than the β domain. More generally, this work provides a foundation for understanding how metallothioneins mediate mercury detoxification in the cell under in vivo conditions.