کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5507045 1536897 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Identification of ligand-selective peptidic ActRIIB-antagonists using phage display technology
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Identification of ligand-selective peptidic ActRIIB-antagonists using phage display technology
چکیده انگلیسی


- Artificial ActRIIB-antagonist peptides were discovered by phage display.
- These peptides selectively bound to the extracellular domain of ActRIIB.
- They antagonized ActRIIB expressed on the cell surface.
- They presented multiple ligand selectivities.

ActRIIB (activin receptor type-2B) is an activin receptor subtype constitutively expressed in the whole body, playing a role in cellular proliferation, differentiation, and metabolism. For its various physiological activities, ActRIIB interacts with activin and multiple other ligands including myostatin (MSTN), growth differentiation factor 11 (GDF11), and bone morphogenetic protein 9 (BMP9). Notably, the protein-protein interaction (PPI) between ActRIIB and MSTN negatively controls muscular development. Therefore, this PPI has been targeted for effective treatment of muscle degenerative diseases such as muscular dystrophy and sarcopenia. Here, we report the identification of ligand-selective peptidic ActRIIB-antagonists by phage display technology. Our peptides bound to the extracellular domain of ActRIIB, inhibited PPIs between ActRIIB expressed on the cell surface and its ligands, and subsequently suppressed activation of Smad that serves as the downstream signal of the ActRIIB pathway. Interestingly, these peptidic antagonists displayed different ligand selectivities; the AR2mini peptide inhibited multiple ligands (activin A, MSTN, GDF11, and BMP9), AR9 inhibited MSTN and GDF11, while AR8 selectively inhibited MSTN. This is the first report of artificial peptidic ActRIIB-antagonists possessing ligand-selectivity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemistry and Biophysics Reports - Volume 11, September 2017, Pages 33-39
نویسندگان
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