Design rules for selective binding of nuclear localization signals to minor site of importin α.

ABSTRACT: Selectivity is a critical issue in molecular recognition. However, design rules that underlie selectivity are often not well understood. Here, we studied five classical nuclear localization signals (NLSs) that contain the motif KRx(W/F/Y)xxAF and selectively bind to the minor site of importin α. The selectivity for the minor site is dissected by building structural models for the NLS-importin α complexes and analyzing the positive design and negative design in the NLSs. In our models, the KR residues of the motif occupy the P1' and P2' pockets of importin α, respectively, forming hydrogen-bonding and cation-π interactions. The aromatic residue at the P4' position plays dual roles in the selectivity for the minor site: by forming π-stacking with W357 of importin α to reinforce the minor-sit

SUBMITTER: Pang X 

PROVIDER: S-EPMC3946659 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature