The CHAD (conserved histidine α-helical) domain has been identified as a specific binding module for inorganic polyphosphates (polyPs), linear polymers of orthophosphate units linked by phosphoanhydride bonds. This binding has been observed in bacterial, archaeal, and eukaryotic CHAD domains, which are formed by two four-helix bundles and possess a central pore surrounded by conserved basic surface … expand

The CHAD (conserved histidine α-helical) domain has been identified as a specific binding module for inorganic polyphosphates (polyPs), linear polymers of orthophosphate units linked by phosphoanhydride bonds. This binding has been observed in bacterial, archaeal, and eukaryotic CHAD domains, which are formed by two four-helix bundles and possess a central pore surrounded by conserved basic surface patches. Different CHAD domains have been found to bind polyPs with dissociation constants ranging from the nano- to mid-micromolar range, but not nucleic acids. The binding of polyPs to CHAD domains occurs across the central pore and along the two basic patches, and mutational analysis of CHAD-polyP interface residues has validated the complex structure. The presence of a CHAD domain in the polyPase ygiF has been shown to enhance its enzymatic activity. Additionally, a CHAD protein from the plant Ricinus communis has been found to localize to the nucleus/nucleolus when expressed in Arabidopsis and tobacco, suggesting that plants may harbor polyPs in these compartments. It has been proposed that CHAD domains may be used to engineer the properties of polyP-metabolizing enzymes and to specifically localize polyP stores in eukaryotic cells and tissues [ PUBMED:31133615 ].

Although the CHAD domain was originally defined as a 'conserved histidine α-helical domain' with histidines acting as metal chelators and/or phosphoacceptors, it has been found that the histidines contributing to Zn2 ion coordination in the RcCHAD structure were not conserved among CHAD family proteins. Therefore, CHAD domains are unlikely to be metal-binding proteins [ PUBMED:31133615 ].