Structural Analysis of Karyopherin-Mediated Nucleocytoplasmic Transport
Zi Chao Zhang and Yuh Min Chook
In human cells, the majority of nucleocytoplasmic transport is mediated by 19 members of the Karyopherinβ (Kapβs/Importins/Exportins) protein family. Thus, Kapβs are critically involved in cellular processes such as gene expression, signal transduction, immune response, oncogenesis and viral propagation, all of which require proper nucleocytoplasmic targeting. Despite the importance of nucleocytoplasmic transport, the mechanisms of transport particularly of nuclear export and the distinctions in targeting signals recognized by the different Kapβ pathways remain poorly understood. Many crystal structures of two different import pathways involving Impβ and Kapβ2 are available and they provide structural explanations for the different steps of nuclear import such substrate recognition, nucleoporin binding and Ran‑mediated substrate dissociation. In contrast, the only available export‑Kapβ structures are of Cse1p and of a fragment of Crm1. In this chapter we will review structures of karyopherins complexed with transport substrates, nucleoporins and the Ran GTPase in both import and export systems and the resulting mechanistic insights from comparative analysis of the current collection of atomic resolution nuclear transport structures.