The histidine phosphotransfer function can be carried out by proteins with at least two different architectures, both composed of a four-helix bundle but differing in the way the bundle is assembled. Most structurally characterized HPt proteins, such as the Hpt domain from the Escherichia coli protein ArcB and the Saccharomyces cerevisiae protein Ypd1, form the bundle as monomers. In the less common type, such as the  Bacillus subtilis sporulation factor Spo0B or the Caulobacter crescentus protein ChpT, the bundle is assembled as a protein dimer, with similarity to the structure of histidine kinases. Monomeric HPt domains possess only one phosphorylatable histidine residue and interact with one response regulator, whereas dimers have two phosphorylation sites and can interact with two response regulators at the same time. Monomeric HPt domains have no enzymatic activity of their own and act purely as phosphate shuttles, while the dimeric Spo0B is catalytic; its phosphotransfer rate to the recipient response regulator is dramatically accelerated compared to histidine phosphate. Despite possessing a second domain with some similarity to ATPase domains, dimeric HPt proteins have not been shown to bind or hydrolyze ATP and lack key residues present in other ATPases.
The monomeric and dimeric forms do not have detectable sequence similarity and are most likely not evolutionarily related; they are instead examples of convergent evolution. Although dimeric HPts likely originate from degenerate histidine kinases, it is possible that monomeric HPts have a number of distinct origins, as there are few evolutionary constraints on the structure.