Importin α

Importin alpha, or karyopherin alpha refers to a class of adaptor proteins that are involved in the import of proteins into the cell nucleus. They are a sub-family of karyopherin proteins.

Importin α is known to bind to the nuclear localization signal (NLS) sequence of nucleus targeted proteins. After this recognition, importin α links the protein to importin β, which transports the NLS-containing protein across the nuclear envelope to its destination. Because of their complementary functional relationship, importin α and importin β are often referred to as the importin α/β heterodimer, but they are functionally separate, and do not normally exist in conjugation with each other, but only associate for cellular import processes, thus importin α proteins constitute an independent class of adaptor protein.

Importin α is a small protein consisting of three functionally distinct domains: the IBB domain, ARM domain, and exportin CAS binding domain.

The N-terminal region of the proteins consists of an importin-β-binding, or IBB, domain. This region of the protein is responsible for interaction with importin β. This region has been described as a series of at least 41 essential amino acid residues, specifically positions 10-50 of the protein. Deletion of a single one of these amino acids has been shown to decrease nuclear import activity by around 50%. Larger deletions correlate with even greater losses of function of the ternary import complex made up of importin α, importin β, and the targeted protein.

The majority of the importin α protein is made up of a series of ten tandem armadillo, or ARM, repeats. A centralized ARM domain, consisting of nine of the ARM repeats, is responsible for regulating the NLS binding to directly interact with nucleus targeted proteins. These ARM repeats recognize the basic residues that are characteristic of NLS sequences. NLS sequences can be monopartite (single cluster of basic amino acids) or bipartite (two clusters of basic amino acids with a linker sequence). The ARM domain contains two binding sites within, allowing a single importin α molecule to interact with two monopartite NLS-containing proteins or a single bipartite NLS protein.

The C-terminus domain of importin α, which include the tenth ARM repeat, is responsible for interacting with exportin CAS, another karyopherin protein that functions in recycling importin α from the nucleus back into the cytoplasm of the cell. The association of this exportin CAS binding domain is Ran-GTP dependent, and hydrolysis of GTP leads to dissociation of importin α from the exportin CAS-Ran complex.

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