ダウンロード数: 195
このアイテムのファイル:
ファイル | 記述 | サイズ | フォーマット | |
---|---|---|---|---|
ncomms11030.pdf | 2.54 MB | Adobe PDF | 見る/開く |
タイトル: | Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance |
著者: | Kabe, Yasuaki Nakane, Takanori Koike, Ikko Yamamoto, Tatsuya Sugiura, Yuki Harada, Erisa Sugase, Kenji https://orcid.org/0000-0001-8623-7743 (unconfirmed) Shimamura, Tatsuro Ohmura, Mitsuyo Muraoka, Kazumi Yamamoto, Ayumi Uchida, Takeshi Iwata, So Yamaguchi, Yuki Krayukhina, Elena Noda, Masanori Handa, Hiroshi Ishimori, Koichiro Uchiyama, Susumu Kobayashi, Takuya Suematsu, Makoto |
著者名の別形: | 小林, 拓也 島村, 達郎 |
キーワード: | Biological sciences Biochemistry Cancer |
発行日: | 18-Mar-2016 |
出版者: | Nature Publishing Group |
誌名: | Nature Communications |
巻: | 7 |
論文番号: | 11030 |
抄録: | Progesterone-receptor membrane component 1 (PGRMC1/Sigma-2 receptor) is a haem-containing protein that interacts with epidermal growth factor receptor (EGFR) and cytochromes P450 to regulate cancer proliferation and chemoresistance; its structural basis remains unknown. Here crystallographic analyses of the PGRMC1 cytosolic domain at 1.95 Å resolution reveal that it forms a stable dimer through stacking interactions of two protruding haem molecules. The haem iron is five-coordinated by Tyr113, and the open surface of the haem mediates dimerization. Carbon monoxide (CO) interferes with PGRMC1 dimerization by binding to the sixth coordination site of the haem. Haem-mediated PGRMC1 dimerization is required for interactions with EGFR and cytochromes P450, cancer proliferation and chemoresistance against anti-cancer drugs; these events are attenuated by either CO or haem deprivation in cancer cells. This study demonstrates protein dimerization via haem-haem stacking, which has not been seen in eukaryotes, and provides insights into its functional significance in cancer. |
著作権等: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
URI: | http://hdl.handle.net/2433/210220 |
DOI(出版社版): | 10.1038/ncomms11030 |
PubMed ID: | 26988023 |
出現コレクション: | 学術雑誌掲載論文等 |
このリポジトリに保管されているアイテムはすべて著作権により保護されています。