Follistatin

Description

Follistatin is a single-chain glycoprotein structurally unrelated to the inhibin and activin proteins. Follistatin binds activin and neutralizes activin action. Follistatin was originally isolated from porcine and bovine follicular fluid for its ability to suppress folliclestimulating hormone (FSH) secretion from the rat pituitary. Subsequently, it was discovered that follistatin binds activin with high affinity.

Physical properties

Mr 35,000 (follistatin 315), 32,000 (follistatin 288). pI 5.0–6.0 (follistatin 315), 8.0–9.0 (follistatin 288). Soluble in water.

Structure and conformation

There are three alternatively spliced products of the single follistatin gene: follistatin 288, follistatin 303, and follistatin 315. Follistatin 288 lacks the carboxyl-terminal Glurich acidic region of follistatin 315. Follistatin 303 is produced by the proteolysis of follistatin 315. Follistatins have two N-linked glycosylation sites, producing different size variants. Follistatins 288 and 315 contain three cysteine-rich follistatin domains of 73–77 aa residues and have a similar binding affinity for activin. Both follistatins have a biding site for heparin and heparan sulfate, a major component of proteoglycans on the cell surface. Follistatin 288 shows high affinity for heparan sulfate and is membrane-bound while follistatin 315 has low affinity for cell-surface proteoglycans and is the predominant form in circulation. Additionally, follistatin-like 3 (follistatin-related protein, FSTL3) consists of two follistatin domains, but lacks the heparin binding site. Two follistatin molecules bind one activin molecule via the activin β-subunits.