1M5I

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

1M5I の概要

• エントリーDOI: 10.2210/pdb1m5i/pdb
• 分子名称: APC protein (2 entities in total)
• 機能のキーワード: coiled-coil, antitumor protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell junction, adherens junction: P25054
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14952.78

構造登録者

Tickenbrock, L.,Cramer, J.,Vetter, I.R.,Mueller, O. (登録日: 2002-07-09, 公開日: 2002-11-20, 最終更新日: 2024-03-13)

主引用文献

Tickenbrock, L.,Cramer, J.,Vetter, I.R.,Muller, O.
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).
J.Biol.Chem., 277:32332-32338, 2002

PubMed 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-(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.

PubMed: 12070164
DOI: 10.1074/jbc.M203990200

実験手法

X-RAY DIFFRACTION (2 Å)