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The coiled coil region (Amino acids 129-250) of the tumor suppressor protein adenomatous polyposis coli (APC) - Its structure and its interaction with chromosome maintenance region 1 (Crm-1)

MPS-Authors

Tickenbrock,  Lara
Max Planck Institute of Molecular Physiology, Max Planck Society;

Cramer,  Janina
Max Planck Institute of Molecular Physiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons98734

Vetter,  Ingrid R.
Abt. I:Mechanistische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons98712

Müller,  Oliver
Sonstige Wissenschaftliche Organisationseinheiten, Max Planck Institute of Molecular Physiology, Max Planck Society;

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Citation

Tickenbrock, L., Cramer, J., Vetter, I. R., & Müller, O. (2002). The coiled coil region (Amino acids 129-250) of the tumor suppressor protein adenomatous polyposis coli (APC) - Its structure and its interaction with chromosome maintenance region 1 (Crm-1). Journal of Biological Chemistry, 277(35): 1, pp. 32332-32338. Retrieved from http://www.jbc.org/cgi/content/abstract/277/35/32332.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0014-0E1E-A
Abstract
The APC (adenomatous polyposis coli) tumor suppressor protein has many different intracellular functions including a nuclear export activity. Only little is known about the molecular architecture of the 2843-amino acid APC protein. Guided by secondary structure predictions we identified a fragment close to the N-terminal end, termed APC-(129-250), as a soluble and protease-resistant domain. We solved the crystal structure of APC-(129-250), which is monomeric and consists of three alpha- helices forming two separate antiparallel coiled coils. APC- (129-250) includes the nuclear export signal NES-(165-174) at the C-terminal end of the first helix. Surprisingly, the conserved hydrophobic amino acids of NES-(165-174) are buried in one of the coiled coils and are thus not accessible for interaction with other proteins. We demonstrate the direct interaction of APC(129-250) with the nuclear export factor chromosome maintenance region 1 (Crm-1). This interaction is enhanced by the small GTPase Ran in its activated GTP-bound form and also by a double mutation in APC-(129250), which deletes two amino acids forming two of the major interhelical interactions within the coiled coil. These observations hint to a regulatory mechanism of the APC nuclear export activity by NES masking.