1m5i

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{{STRUCTURE_1m5i| PDB=1m5i | SCENE= }}
{{STRUCTURE_1m5i| PDB=1m5i | SCENE= }}
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'''Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC'''
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===Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC===
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==Overview==
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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-(129-250), 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.
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(as it appears on PubMed at http://www.pubmed.gov), where 12070164 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12070164}}
==Disease==
==Disease==
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[[Category: Vetter, I R.]]
[[Category: Vetter, I R.]]
[[Category: Coiled-coil]]
[[Category: Coiled-coil]]
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Revision as of 20:15, 2 July 2008

Image:1m5i.png

Template:STRUCTURE 1m5i

Contents

Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC

Template:ABSTRACT PUBMED 12070164

Disease

Known disease associated with this structure: Adenoma, periampullary OMIM:[611731], Adenomatous polyposis coli OMIM:[611731], Brain tumor-polyposis syndrome 2 OMIM:[611731], Colorectal cancer, somatic OMIM:[611731], Desmoid disease, hereditary OMIM:[611731], Gardner syndrome OMIM:[611731], Gastric cancer, somatic OMIM:[611731], Hepatoblastoma OMIM:[611731]

About this Structure

1M5I is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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)., Tickenbrock L, Cramer J, Vetter IR, Muller O, J Biol Chem. 2002 Aug 30;277(35):32332-8. Epub 2002 Jun 17. PMID:12070164

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