1m5i

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spinqualitylabelsall models 1m5i, resolution 2.0Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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 Feb 21 13:51:46 2008