Structure-function relationships in the NA+,K+-pump.

Abstract

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 alphabeta heterodimer. All known enzymatic functions of the pump occur through the alpha subunit. Although necessary for activity, the complete role of the beta subunit is not understood fully. Numerous studies have established that the alphabeta protomer is the minimal functional unit needed to perform the Albers-Post reaction cycle. However, higher orders of aggregation [(alphabeta)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 alpha subunit and the Ca2+ATPase (a closely related P-type ATPase). The spatial location of the beta 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.