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ID 114782
著者
Chen, Yi-An National Institute of Biomedical Innovation
Murakami, Yoichi National Institute of Biomedical Innovation|Tohoku University
Ahmad, Shandar National Institute of Biomedical Innovation
Mizuguchi, Kenji National Institute of Biomedical Innovation
キーワード
Breast cancer
Estrogen receptor-alpha
BIG3
PHB2
Protein-protein interaction
Bioinformatics
資料タイプ
学術雑誌論文
抄録
Background: Brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3) has been identified recently as a novel regulator of estrogen signalling in breast cancer cells. Despite being a potential target for new breast cancer treatment, its amino acid sequence suggests no association with any well-characterized protein family and provides little clues as to its molecular function. In this paper, we predicted the structure, function and interactions of BIG3 using a range of bioinformatic tools.
Results: Homology search results showed that BIG3 had distinct features from its paralogues, BIG1 and BIG2, with a unique region between the two shared domains, Sec7 and DUF1981. Although BIG3 contains Sec7 domain, the lack of the conserved motif and the critical glutamate residue suggested no potential guaninyl-exchange factor (GEF) activity. Fold recognition tools predicted BIG3 to adopt an α-helical repeat structure similar to that of the armadillo (ARM) family. Using state-of-the-art methods, we predicted interaction sites between BIG3 and its partner PHB2.
Conclusions: The combined results of the structure and interaction prediction led to a novel hypothesis that one of the predicted helices of BIG3 might play an important role in binding to PHB2 and thereby preventing its translocation to the nucleus. This hypothesis has been subsequently verified experimentally.
掲載誌名
BMC Research Notes
ISSN
17560500
出版者
BioMed Central|Springer Nature
7
開始ページ
435
発行日
2014-07-06
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
先端酵素学研究所