Role of metal in folding and stability of copper proteins in vitro.
Metal coordination is required for function of many proteins. For biosynthesis of proteins coordinating a metal, the question arises if the metal binds before, during or after folding of the polypeptide. Moreover, when the metal is bound to the protein, how does its coordination affect biophysical properties such as stability and dynamics? Understanding how metals are utilized by proteins in cells on a molecular level requires accurate descriptions of the thermodynamic and kinetic parameters involved in protein-metal complexes. Copper is one of the essential transition metals found in the active sites of many key proteins. To avoid toxicity of free copper ions, living systems have developed elaborate copper-transport systems that involve dedicated proteins that facilitate efficient and specific delivery of copper to target proteins. This review describes in vitro and in silico biophysical work assessing the role of copper in folding and stability of copper-binding proteins. Examples of proteins discussed are: a blue-copper protein (Pseudomonas aeruginosa azurin), members of copper-transport systems (bacterial CopZ, human Atox1 and ATP7B domains) and multi-copper ferroxidases (yeast Fet3p and human ceruloplasmin). The consequences of interactions between copper proteins and platinum-complexes are also discussed. This article is part of a Special Issue entitled: Cell Biology of Metals.
Chemistry Department, Chemical Biological Center, Umeå University, 90187 Umeå, Sweden.
Maria E
ME
Palm-Espling
Moritz S
MS
Niemiec
Pernilla
P
Wittung-Stafshede
D001419:Bacteria; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D002570:Ceruloplasmin / Q000737:chemistry* / Q000378:metabolism; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D000079922:Copper Transport Proteins; D006801:Humans; D007700:Kinetics; D056511:Metallochaperones; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D017510:Protein Folding; D055550:Protein Stability; D013816:Thermodynamics; D015003:Yeasts
C474500:ATOX1 protein, human; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D056831:Coordination Complexes; D000079922:Copper Transport Proteins; D056511:Metallochaperones; D018832:Molecular Chaperones; C023548:copper-binding protein; D003300:Copper; D002570:Ceruloplasmin