Structure-Function Relationships in the Na⁺,K⁺-Pump

The Na,K-pump was discovered about 50 years ago. Since then there has been a methodic investigation of its structure and functional characteristics. The development of the Albers-Post model for the transport cycle was a milestone that provided the framework for detailed understanding of the transport process. The pump is composed of 2 subunits that exist in the membrane as an αβ heterodimer. All known enzymatic functions of the pump occur through the α subunit. Although necessary for activity, the complete role of the β subunit is not understood fully. Numerous studies have established that the αβ protomer is the minimal functional unit needed to perform the Albers-Post reaction cycle. However, higher orders of aggregation [(αβ)_n] are commonly detected. There is little evidence that oligomerization has functional consequence for ion transport. The Na⁺,K⁺-adenosine triphosphatase (ATPase) is a member of the P-type ATPase family of transporters. Proteins within this family have common amino acid sequence motifs that share functional characteristics and structure. Low-resolution 3-dimensional reconstruction of 2-dimensional crystal diffractions provide evidence for the similarity in tertiary structure of the α subunit and the Ca²⁺ATPase (a closely related P-type ATPase). The spatial location of the β subunit also is obvious in these reconstructions. Recent high-resolution reconstructions from 3-dimensional crystals of the Ca²⁺ATPase provide structural details at the atomic level. It now is possible to interpret structurally some of the key steps in the Albers-Post reaction. Some of these high-resolution interpretations are translatable to the Na⁺,K⁺-ATPase, but a high-resolution structure of the Na,K-pump is needed for the necessary details of those aspects that are unique to this transporter.

Keywords:  Na⁺ , K⁺-ATPase , Na , K pump , structure , Na(+)-K(+)–exchanging ATPase