<p>CutA1 is a widespread protein of about 12kDa found in bacteria, plants, and animals, including humans [<cite idref="PUB00014093"/>]. The protein was originally identified in a gene locus of<taxon tax_id="562">Escherichia coli</taxon> called cutA involved in divalent metal tolerance[<cite idref="PUB00007506"/>]. The cutA locus consists of two operons, one containing a single gene encoding a cytoplasmicprotein, CutA1, and the other composed of two genes encoding a 50kDa (CutA2) and a 24kDa (CutA3) inner membrane proteins. Molecular genetics studies on theE. coli cutA locus showed that some mutations lead to copper sensitivity due to its increased uptake [<cite idref="PUB00007507"/>]. However, the specific function of CutA1 in E. coli is stillunknown. </p><p> However, a possible role of mammalian CutA1 in the anchoring of the enzymeacetylcholinesterase (AChE)1 in neuronal cell membranes. CutA1 does not directly interact with AChE, but the CutA1 gene is widely expressed in different regions of the brain with an expressionpattern that parallels that of AChE. In addition CutA1 Co-purified with AChE from human caudate nucleus. CutA1, thus, might provide an intriguing link between copper tolerance in bacteria and acomplex process in the brain of the most evolved organisms. </p><p> Both rat and E. coli CutA1 have been crystallised [<cite idref="PUB00014093"/>]. Bothproteins are trimeric in the crystals and in solution through an inter-subunit beta-sheet formation. Each monomer exhibits the same overall structure, adopting a ferredoxin-like fold made of an alpha-beta sandwich with antiparallel beta-sheet and containing an additional short strand and a C-terminal helix. In the beta-sheet, alternate strands are connected by helices with positive crossovers, resulting in a double beta-alpha-beta motifwhere the antiparallel beta-sheet packs against antiparallel alpha-helices. The C-terminal helix packs orthogonal to the N terminus. </p><p>The strong structure similarity of CutA1 with PII proteins might point to an role for CutA1 in signalling through allosteric communication between monomers. CutA1 may be involved in the tuning of a disulphide bond cascade in bacteria and mammals, acting as the PII proteins do in the nitrogen signal cascade in bacteria and plants.</p>