Limits...
Allosteric control of the exportin CRM1 unraveled by crystal structure analysis.

Monecke T, Dickmanns A, Ficner R - FEBS J. (2014)

Bottom Line: Moreover, during the last decade, CRM1 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 CRM1, Ran and cargo is a prerequisite for the development of highly effective drugs.Here we review recent structural advances in the characterization of CRM1 and CRM1-containing complexes with a special emphasis on X-ray crystallographic studies.

View Article: PubMed Central - PubMed

Affiliation: Abteilung für Molekulare Strukturbiologie, Institut für Mikrobiologie und Genetik, Göttinger Zentrum für Molekulare Biowissenschaften, Georg-August-Universität Göttingen, Germany.

Show MeSH

Related in: MedlinePlus

Schematic overview of the individual steps and conformational changes during a CRM1 export cycle. The steps depicted highlight the different states of CRM1 (wheat) with respect to the overall shape as well as the positions of the acidic loop (light green), the C-terminal helix (HEAT helix 21B, blue) and the conformation of the NES cleft (red) during the transport cycle. The dashed line emanating from free CRM1 indicates its high structural flexibility. See main text for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4231977&req=5

fig07: Schematic overview of the individual steps and conformational changes during a CRM1 export cycle. The steps depicted highlight the different states of CRM1 (wheat) with respect to the overall shape as well as the positions of the acidic loop (light green), the C-terminal helix (HEAT helix 21B, blue) and the conformation of the NES cleft (red) during the transport cycle. The dashed line emanating from free CRM1 indicates its high structural flexibility. See main text for details.

Mentions: The available structural information on CRM1 and its various export and disassembly complexes allowed the deduction of a detailed flowchart with the gross overall movements as well as the important interaction sites with Ran, cargo and disassembly factors (RanBPs) in the individual steps of a CRM1 transport cycle (Fig.7).


Allosteric control of the exportin CRM1 unraveled by crystal structure analysis.

Monecke T, Dickmanns A, Ficner R - FEBS J. (2014)

Schematic overview of the individual steps and conformational changes during a CRM1 export cycle. The steps depicted highlight the different states of CRM1 (wheat) with respect to the overall shape as well as the positions of the acidic loop (light green), the C-terminal helix (HEAT helix 21B, blue) and the conformation of the NES cleft (red) during the transport cycle. The dashed line emanating from free CRM1 indicates its high structural flexibility. See main text for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231977&req=5

fig07: Schematic overview of the individual steps and conformational changes during a CRM1 export cycle. The steps depicted highlight the different states of CRM1 (wheat) with respect to the overall shape as well as the positions of the acidic loop (light green), the C-terminal helix (HEAT helix 21B, blue) and the conformation of the NES cleft (red) during the transport cycle. The dashed line emanating from free CRM1 indicates its high structural flexibility. See main text for details.
Mentions: The available structural information on CRM1 and its various export and disassembly complexes allowed the deduction of a detailed flowchart with the gross overall movements as well as the important interaction sites with Ran, cargo and disassembly factors (RanBPs) in the individual steps of a CRM1 transport cycle (Fig.7).

Bottom Line: Moreover, during the last decade, CRM1 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 CRM1, Ran and cargo is a prerequisite for the development of highly effective drugs.Here we review recent structural advances in the characterization of CRM1 and CRM1-containing complexes with a special emphasis on X-ray crystallographic studies.

View Article: PubMed Central - PubMed

Affiliation: Abteilung für Molekulare Strukturbiologie, Institut für Mikrobiologie und Genetik, Göttinger Zentrum für Molekulare Biowissenschaften, Georg-August-Universität Göttingen, Germany.

Show MeSH
Related in: MedlinePlus