Beyond bilobal: transferrin homologs having unusual domain architectures.

BACKGROUND

Most transferrin family proteins have a familiar bilobal structure, the result of an ancient gene duplication, with an iron binding site in each of two homologous lobes. Scattered throughout the evolutionary tree from algae to mammals, though, are transferrin homologs having other kinds of domain architectures.

SCOPE OF REVIEW

This review covers a variety of unusual transferrin forms, including monolobals, bilobals with one or both iron-binding sites abrogated, bilobals accessorized with long insertions or with membrane anchors, and even trilobals. The monolobal transferrin homologs from marine invertebrate ascidians are especially highlighted here.

MAJOR CONCLUSIONS

Unusual transferrin homologs appear scattered through much of the evolutionary tree. For some of these proteins, iron binding and/or iron transport appear to be the primary roles; for others they clearly are not. Many are incompletely or not at all studied.

GENERAL SIGNIFICANCE

Taken together, these proteins begin to offer a glimpse into how the transferrin architecture has been repurposed for a diversity of applications. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders.