FC0001
nucleoplasmin NLS  -  Importin-α

Biological function
Nuclear localization signals (NLS) facilitate the transport of proteins into the nucleus.

Structural evidence
Bipartite binding mode of the mammalian NLS is achieved via two basic clusters of the NLS, which are connected by a poorly ordered linker (10-12 residues). Electron density maps evidence the peptide binding simultaneously in alternative modes (registers): in the vicinity of the P₅, P₁ (alternative rotamers), P₆ (staggering of KKKK cluster one position C-terminally) and P-P₃₄ (staggering of KR cluster two positions C-terminally) positions.

Biochemical evidence
The poorly ordered linker (10-12 residues) is tolerant to mutations.

Mechanism category
tethering

Isoforms, context-dependence
The fuzzy linker modulates specificities of different importin - α isoforms for different cargo proteins.

Significance
The fuzzy linker may account for diverse NLS binding by the same receptor.