RT Journal Article
SR Electronic
T1 Molecular characterization of CHAD domains as inorganic polyphosphate-binding modules
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900385
DO 10.26508/lsa.201900385
VO 2
IS 3
A1 Laura Lorenzo-Orts
A1 Ulrich Hohmann
A1 Jinsheng Zhu
A1 Michael Hothorn
YR 2019
UL https://www.life-science-alliance.org/content/2/3/e201900385.abstract
AB Inorganic polyphosphates (polyPs) are linear polymers of orthophosphate units linked by phosphoanhydride bonds. Here, we report that bacterial, archaeal, and eukaryotic conserved histidine α-helical (CHAD) domains are specific polyP-binding modules. Crystal structures reveal that CHAD domains are formed by two four-helix bundles, giving rise to a central pore surrounded by conserved basic surface patches. Different CHAD domains bind polyPs with dissociation constants ranging from the nano- to mid-micromolar range, but not nucleic acids. A CHAD—polyP complex structure reveals the phosphate polymer binding across the central pore and along the two basic patches. Mutational analysis of CHAD—polyP interface residues validates the complex structure. The presence of a CHAD domain in the polyPase ygiF enhances its enzymatic activity. The only known CHAD protein from the plant Ricinus communis localizes to the nucleus/nucleolus when expressed in Arabidopsis and tobacco, suggesting that plants may harbor polyPs in these compartments. We propose 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.