Portrait of author

Pin Lyu:
Structural and functional analysis of PIB-type ATPases

Date: 09-03-2022    Supervisor: Per Amstrup Pedersen & Pontus Emanuel Gourdon



Heavy metal ions act as cofactors participating in many enzymatic reactions. Improper cellular metal concentrations lead to cell death, plant withering, and human diseases. Heavy metal transporters play a key role for the maintenance of such levels in the cell.

PIB-ATPases are a large subfamily that transfer heavy metal ions and are responsible for metal detoxification. In cells, ZntA, a divalent metal transporter from E.coli (EcZntA), recognizes and mediates Pb2+, Zn2+, and Cd2+ detoxification. The exported metal ions can be absorbed by hyperaccumulators that translocate them from root to shoot and reduce toxic contamination in soil. In humans, a representative of the PIB-type ATPases, ATP7B, is linked to the transport of excess copper to the bile, and mutations of ATP7B lead to Wilson’s disease.

Moreover, the PIB-type ATPases can serve as cofactors for assembling enzymes to maintain metal homeostasis and keep regular homeostasis. For instance, there are two Cu+-ATPases in Pseudomonas aeruginosa; CopA1 and CopA2. CopA1 has a vital role in metal detoxification, whereas CopA2 is associated with cytochrome c oxidase assembly and responds to oxidative stressor. Structural-functional analysis of the PIB pumps can reveal their molecular mechanisms and increase understanding of the metal transport process, opening new insight into the molecular pathophysiology of human diseases and developing novel drugs.