Identification of ion-selectivity determinants in heavy-metal transport P1B-type ATPases.

摘要: P1B-type ATPases transport a variety of metals (Cd2+, Zn2+, Pb2+, Co2+, Cu2+, Ag+, Cu+) across biomembranes. Characteristic sequences CP[C/H/S] in transmembrane fragment H6 were observed the putative transporting metal site founding members this subfamily (initially named CPx-ATPases). In spite their importance for homeostasis and biotolerance, mechanisms ion selectivity are not understood. Studies better-characterized P(II)-type (Ca-ATPase Na,K-ATPase) have identified three segments that participate binding transport. Testing hypothesis specificity is determined by conserved amino acids located equivalent (H6, H7, H8), 234 P1B-ATPase protein analyzed. This showed although contains characteristic CPX or XPC sequences, H7 H8 provide signature predict each five subgroups identified. These invariant contain diverse side chains (thiol, hydroxyl, carbonyl, amide, imidazolium) can transient coordination during consequently determine particular enzyme. Each subgroup shares additional structural characteristics such as presence (or absence) amino-terminal metal-binding domains number segments. differences suggest unique functional addition to specificity.