In:
The FEBS Journal, Wiley, Vol. 281, No. 18 ( 2014-09), p. 4179-4194
Abstract:
Nucleocytoplasmic trafficking in eukaryotic cells is a highly regulated and coordinated process which involves an increasing variety of soluble nuclear transport receptors. Generally, transport receptors specifically bind their cargo and facilitate its transition through nuclear pore complexes, aqueous channels connecting the two compartments. Directionality of such transport events by receptors of the importin β superfamily requires the interaction with the small GTP ase Ras‐related nuclear antigen (Ran). While importins need Ran GTP to release their cargo in the nucleus and thus to terminate import, exportins recruit cargo in the Ran GTP ‐bound state. The exportin chromosome region maintenance 1 ( CRM 1) is a highly versatile transport receptor that exports a plethora of different protein and RNP cargoes. Moreover, binding of Ran GTP and of cargo to CRM 1 are highly cooperative events despite the fact that cargo and Ran GTP do not interact directly in crystal structures of assembled export complexes. Integrative approaches have recently unraveled the individual steps of the CRM 1 transport cycle at a structural level and explained how the HEAT ‐repeat architecture of CRM 1 provides a framework for the key elements to mediate allosteric interactions with Ran GTP , Ran binding proteins and cargo. Moreover, during the last decade, CRM 1 has become a more and more appreciated target for anti‐cancer drugs. Hence, detailed understanding of the flexibility, the regulatory features and the positive binding cooperativity between CRM 1, Ran and cargo is a prerequisite for the development of highly effective drugs. Here we review recent structural advances in the characterization of CRM 1 and CRM 1‐containing complexes with a special emphasis on X‐ray crystallographic studies.
Type of Medium:
Online Resource
ISSN:
1742-464X
,
1742-4658
DOI:
10.1111/febs.2014.281.issue-18
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2172518-4
SSG:
12
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