Membrane Anchoring and Ion-Entry Dynamics in P-type ATPase Copper Transport.

ABSTRACT: Cu⁺-specific P-type ATPase membrane protein transporters regulate cellular copper levels. The lack of crystal structures in Cu⁺-binding states has limited our understanding of how ion entry and binding are achieved. Here, we characterize the molecular basis of Cu⁺ entry using molecular-dynamics simulations, structural modeling, and in vitro and in vivo functional assays. Protein structural rearrangements resulting in the exposure of positive charges to bulk solvent rather than to lipid phosphates indicate a direct molecular role of the putative docking platform in Cu⁺ delivery. Mutational analyses and simulations in the presence and absence of Cu⁺ predict that the ion-entry path involves two ion-binding sites: one transient Met148-Cys3

SUBMITTER: Gronberg C 

PROVIDER: S-EPMC5153542 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature