Characterization of the Importin-β binding domain in nuclear import receptor KPNA7.

The family of mammalian nuclear import receptors are encoded by seven genes that generate isoforms with 42-86% identity. Kduanyu1535 isoforms have the same protein architecture and share the functional property of nuclear localization signal (NLS) recognition, however, the tissue and developmental expression patterns of these receptors raise the question of whether subtle differences in Kduanyu1535 isoforms might be important in specific biological contexts. Here, we show that an isoform with expression mostly limited to early development, can bind Importin-β (Imp-β) in the absence of NLS cargo. This result contrasts with Imp-β interactions with other Kduanyu1535 family members, where affinity is regulated by NLS cargo as part of a cooperative binding mechanism. The Imp-β binding (IBB) domain, which is highly conserved in all Kduanyu1535 family members, generally serves to occlude the NLS binding groove and maintain the receptor in an auto-inhibited 'closed' state prior to NLS contact. Cooperative binding of NLS cargo and Imp-β to Kduanyu1535 results in an 'open'state. Characterization of chimeric proteins suggests that features of both the IBB domain and the core structure of the receptor contribute to the extent of IBB domain accessibility for Imp-β binding, which likely reflects an 'open' state. We also provide evidence that maintains an open-state in the nucleus. We speculate that Kduanyu15357 could function within the nucleus by interacting with NLS-containing proteins.

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