Publication: Research - peer-review › Journal article – Annual report year: 2012
Metallothioneins (MT) are small, metal-binding proteins with diverse functions related to metal ion homeostasis. This paper presents the full 384–388-atom structures of the two native Zn(II)- and the Cd(II)-containing domains of human MT2, optimized with density functional theory. The presented structures are accurate to ~0.03Å for bond lengths and thus provide new physical insight into the detailed electronic structures of MTs, in particular with accurate accounts of bridging vs. terminal bonds not available from NMR or EXAFS. The MT protein enhances the asymmetry, as compared to the protein-free clusters, causing a hierarchy in binding that most likely allows MTs to transfer ions to multiple targets in vivo. The protein polarization is substantial and occurs primarily via the terminal sulfurs, a key mechanism in providing domain-specific electronic structures. The β-domain polarizes its smaller cluster less on average, due to its less polarizable, higher negative charge density, as reflected in longer M&sbnd;S bond lengths and smaller bond orders. This may explain why MT2β is more reactive and dynamic and why MTs have evolved two different-size, asymmetric domains with different metal binding affinities fit for different molecular targets of metal ion transfer.
|Citations||Web of Science® Times Cited: 4|
- Protein structure, Coordination chemistry, DFT, Metallothionein, Zn, Cd