This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1m5i
From Proteopedia
| |||||||
| , resolution 2.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | APC (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC
Contents |
Overview
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.
Disease
Known diseases 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
Page seeded by OCA on Thu Mar 20 12:39:08 2008
