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-type ATPases are a large subfamily of P-type ATPases that transport heavy metal ions. Exploring the PIB-type ATPases would clarify the mechanism of metal ions transport and provide the theoretical basis for practical applications, e.g., designing new inhibitors for drug discovery and biological sequestration of heavy metal ions to reduce contaminated soils. This thesis aims to understand the molecular mechanisms of PIB-type ATPases. The objectives include: 1) elucidating the mechanisms of metal ions uptake, loading, and binding by obtaining structures generated in the presence of metal; 2) investigating the structure and function of the variable N-terminal regions composed of heavy-metal-binding domains (HMBDs) and metal-binding residues (e.g., histidine-rich stretches); and 3) understanding the overall architecture and cargo transport pathway of the poorly understood PIB-4-type ATPases. We applied X-ray crystallography combined with biochemical experiments to achieve the goals. In my thesis, we first clarified the mechanism of metal ions uptake, an initiating process within the transport pathways. Using an established model PIB-1-type ATPases, AfCopA, we revealed that Cu+ uptake is assisted by a conserved methionine, shuttling the metal from CopZ metallochaperones. In contrast, the PIB-2 and PIB-4-type ATPases, MmCadA and sCoaT, rely negatively charged surfaces for metal uptake of for example Zn2+ and Co2+. We further provide the structure of the unusual N-terminal HMBD of the PIB-1-type ATPase LpCopA. We identified a metal-binding site by comparing metal-bound and metal-free states. In addition, our functional data point towards that HMBDs in the PIB-1 and PIB-2-type ATPases can act as a sensors that regulates the arrangement of the distal N-terminal part of the termini. In addition, the function of the proximal metal-binding residues (e.g., histidine-rich stretch), specifically present in certain PIB-2type ATPases, was clarified. We propose such sequences are analogous to Cu+ metallochaperones that directly delivers the metal ions to its transmembrane site. Finally, we identified the overall architecture and the transport mechanisms of the PIB-4-type ATPases, sCoaT. PIB-4-type ATPases share an architecture with three cytosolic and eight transmembrane segments - similar to the PIB-1 and PIB-2-type ATPases, but do not contain a classical HMBD. In addition, the conformational changes of sCoaT in the catalytic reaction cycle and its unique regulatory mechanism are illustrated.