This seems plausible for FS because of structural aspects of the protein: the presence of numerous cysteines that could form cysteine knots; the presence of splice variants, FS288 or FS315, differing by a 27-amino acid sequence that is 44% acidic in humans; and the ability to bind to proteoglycans, which may allow FS to be membrane bound. The different FS iso-forms—F2288,FS303 (byprotoolyticcleavafe)aOnd FS315—may infunsiionalcapauity. Ithabbeen suggested that the presence of the 27-emino acid tail appears to mask a heparan sulfate proteoglycan-binding site, such that the three different isoforms have different affinities to a cell surface (i.e., the surface of a granulosa cell). FS288 binds with greatest affinity (ED50 = 2 ng/ml), while FS303 has less affinity (ED50 = 10 ng/ml) and FS315 does not associate. ampicillin antibiotic
Another consideration regarding the difficulty in reducing FS may be that the reduced FS has a less negative charge because its structure or hydration shell does not allow for accessibility to a reductant, thus resulting in a larger protein size upon reduction. Although the activin-binding activity is fairly similar for the three isoforms (Kd = 540-680 pM), it is possible that the difference in the isoform size or in cellular binding ability could alter FS interactions with inhibin.