title: Lessons on the critical interplay between zinc binding and protein structure and dynamics.
abstract: Zinc is one of the most important micronutrients for virtually all living organisms, and hence, it is important to understand the molecular mechanisms for its homeostasis. Besides proteins involved in transmembrane transport, both extra- and intracellular zinc-binding proteins play important roles in the respective metabolic networks. Important examples for extracellular zinc transporters are mammalian serum albumins, and for intracellular zinc handling, certain metallothioneins are of relevance. The availability of protein structures including relevant metal binding sites is a fundamental prerequisite to decipher the mechanisms that govern zinc binding dynamics in these proteins, but their determination can prove to be surprisingly challenging. Due to the spectroscopic silence of Zn(2+), combinations of biophysical techniques including electrospray ionisation mass spectrometry (ESI-MS) and multinuclear NMR, isothermal titration calorimetry (ITC) and extended X-ray absorption fine structure (EXAFS) spectroscopy, coupled with site-directed mutagenesis and molecular modelling have proven to be valuable approaches to understand not only the zinc-binding properties of metallothioneins and albumins, but also the influence of other physiologically relevant competing agents. These studies have demonstrated why the bacterial metallothionein SmtA contains a site inert towards exchange with Cd(2+), why the plant metallothionein EC from wheat is partially unfolded in the presence of Cd(2+), and how fatty acids impact on the zinc-binding ability of mammalian serum albumins.
authors: Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK. c.blindauer@warwick.ac.uk
authors: Claudia A
authors: CA
authors: Blindauer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites; D002104:Cadmium / Q000737:chemistry; D006801:Humans; D008668:Metallothionein / Q000737:chemistry* / Q000235:genetics; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry* / Q000235:genetics; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry* / Q000235:genetics; D046940:Synechococcus / Q000737:chemistry; D014908:Triticum / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D010940:Plant Proteins; D012709:Serum Albumin; C080048:smtA protein, Synechococcus; D002104:Cadmium; D008668:Metallothionein; D015032:Zinc