Metal-binding protein explained

Metal-binding proteins are proteins or protein domains that chelate a metal ion.^[1]

Binding of metal ions via chelation is usually achieved via histidines or cysteines. In some cases this is a necessary part of their folding and maintenance of a tertiary structure. Alternatively, a metal-binding protein may maintain its structure without the metal (apo form) and bind it as a ligand (e.g. as part of metal homeostasis). In other cases a coordinated metal cofactor is used in the active site of an enzyme to assist catalysis.

Histidine-rich metal-binding proteins

Poly-histidine tags (of six or more consecutive His residues) are utilized for protein purification by binding to columns with nickel or cobalt, with micromolar affinity.^[2] Natural poly-histidine peptides, found in the venom of the viper Atheris squamigera have been shown to bind Zn(2+), Ni(2+) and Cu(2+) and affect the function of venom metalloproteases.^[3] Furthermore, histidine-rich low-complexity regions are found in metal-binding and especially nickel-cobalt binding proteins.^[4] These histidine-rich low complexity regions have an average length of 36 residues, of which 53% histidine, 23% aspartate, 9% glutamate. Intriguingly, structured domains with metal binding properties also have very similar frequencies of these amino acids that are involved in the coordination of the metal.^[5] Accordingly, it has been hypothesized that these metal-binding structured domains could have originated and evolved/optimized from metal-binding low-complexity protein regions of similar amino acid content.

References

1. Berg. J. M.. 1990-04-25. Zinc fingers and other metal-binding domains. Elements for interactions between macromolecules. The Journal of Biological Chemistry. 265. 12. 6513–6516. 10.1016/S0021-9258(19)39172-0 . 0021-9258. 2108957. free .
2. Book: Bornhorst. J. A.. Falke. J. J.. Purification of proteins using polyhistidine affinity tags . 2000. Applications of Chimeric Genes and Hybrid Proteins Part A: Gene Expression and Protein Purification. Methods in Enzymology. 326. 245–254. 10.1016/s0076-6879(00)26058-8. 0076-6879. 2909483. 11036646. 978-0-12-182227-9 .
3. Watly. Joanna. Simonovsky. Eyal. Barbosa. Nuno. Spodzieja. Marta. Wieczorek. Robert. Rodziewicz-Motowidlo. Sylwia. Miller. Yifat. Kozlowski. Henryk. 2015-08-17. African Viper Poly-His Tag Peptide Fragment Efficiently Binds Metal Ions and Is Folded into an α-Helical Structure. Inorganic Chemistry. 54. 16. 7692–7702. 10.1021/acs.inorgchem.5b01029. 1520-510X. 26214303.
4. Ntountoumi. Chrysa. Vlastaridis. Panayotis. Mossialos. Dimitris. Stathopoulos. Constantinos. Iliopoulos. Ioannis. Promponas. Vasilios. Oliver. Stephen G. Amoutzias. Grigoris D. 2019-11-04. Low complexity regions in the proteins of prokaryotes perform important functional roles and are highly conserved. Nucleic Acids Research. en. 47. 19. 9998–10009. 10.1093/nar/gkz730. 0305-1048. 6821194. 31504783.
5. Dokmanić. Ivan. Sikić. Mile. Tomić. Sanja. March 2008. Metals in proteins: correlation between the metal-ion type, coordination number and the amino-acid residues involved in the coordination. Acta Crystallographica. Section D, Biological Crystallography. 64. Pt 3. 257–263. 10.1107/S090744490706595X. 0907-4449. 18323620.