Follistatin
FunctionFollistatin (Fs1) is a follicle-stimulating hormone inhibiting substance present in ovarian follicular fluid. Fs1 has affinity for Activin which is neutralized upon binding to Fs1. The interplay between Fs1 and activin represents a regulatory mechanism which affects a variety of cellular processes[1]. Follistatin-like protein (Fstl) is highly homologous to Fs1 and binds activin and myostatin but does not contain a heparin-binding motif. Fst contains 2 follistatin domains - containing 10 Cys residues - while Fs1 contains 3 such domains[2]. RelevanceFs1 binds myostatin and inhibits its function. Myostatin acts to limit skeletal muscle mass. Thus, the regulation of activin and myostatin by Fs1 may provide therapeutic targets for preserving muscle mass and prevent muscle atrophy and degeneration[3]. Fstl-1 can prevent myocardial ischemia injury by inhibiting apoptosis and inflammatory response and can represent a therpeutic target for post-myocardial infraction[4]. Structural highlightsThe 3D structure of the complex between follistatin-like 3 and activin shows the . The between the two proteins include those in the FSTL-3 N-terminal domain and hydrogen bonds in the FSTL-3 follistatin domain[5].
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3D structures of follistatin3D structures of follistatin
Updated on 29-July-2021
ReferencesReferences
- ↑ Phillips DJ, de Kretser DM. Follistatin: a multifunctional regulatory protein. Front Neuroendocrinol. 1998 Oct;19(4):287-322. doi: 10.1006/frne.1998.0169. PMID:9799587 doi:http://dx.doi.org/10.1006/frne.1998.0169
- ↑ Tortoriello DV, Sidis Y, Holtzman DA, Holmes WE, Schneyer AL. Human follistatin-related protein: a structural homologue of follistatin with nuclear localization. Endocrinology. 2001 Aug;142(8):3426-34. PMID:11459787
- ↑ Lee SJ, Lee YS, Zimmers TA, Soleimani A, Matzuk MM, Tsuchida K, Cohn RD, Barton ER. Regulation of muscle mass by follistatin and activins. Mol Endocrinol. 2010 Oct;24(10):1998-2008. doi: 10.1210/me.2010-0127. Epub 2010, Sep 1. PMID:20810712 doi:http://dx.doi.org/10.1210/me.2010-0127
- ↑ Ogura Y, Ouchi N, Ohashi K, Shibata R, Kataoka Y, Kambara T, Kito T, Maruyama S, Yuasa D, Matsuo K, Enomoto T, Uemura Y, Miyabe M, Ishii M, Yamamoto T, Shimizu Y, Walsh K, Murohara T. Therapeutic impact of follistatin-like 1 on myocardial ischemic injury in preclinical models. Circulation. 2012 Oct 2;126(14):1728-38. doi: 10.1161/CIRCULATIONAHA.112.115089. , Epub 2012 Aug 28. PMID:22929303 doi:http://dx.doi.org/10.1161/CIRCULATIONAHA.112.115089
- ↑ Stamler R, Keutmann HT, Sidis Y, Kattamuri C, Schneyer A, Thompson TB. The structure of FSTL3.activin A complex. Differential binding of N-terminal domains influences follistatin-type antagonist specificity. J Biol Chem. 2008 Nov 21;283(47):32831-8. Epub 2008 Sep 2. PMID:18768470 doi:10.1074/jbc.M801266200