Fetuin-B

The plasma protein Fetuin-B is essential for the fertilization of mammalian oocytes. As an inhibitor of the oocyte-specific proteinase ovastacin, Fetuin-B maintains the fertilization ability of the oocyte. Consequently, Fetuin-B deficient mice are infertile. The oocytes of these animals show premature hardening of the zona pellucida (extracellular matrix surrounding the oocyte). Sperm are therefore unable to fertilize this oocyte. We measure Fetuin-B serum levels in humans and investigate the influence of Fetuin-B on oocyte fertilization ability in vitro and in vivo in a mouse model. Through structural analyses, we determine the domain of Fetuin-B that is essential for the inhibition of ovastacin. Thus, we are laying the foundation for potential therapies for patients with previously unexplained infertility, as well as for potential non-hormonal contraceptives.

Recently, we elucidated the exact interaction mechanism of fetuin-B and ovastacin using a 3-dimensional structural model.

Structural model of fetuin-B complex with astacin. Fetuin-B consists of a cystatin-like domain 1 (green), a cystatin-like domain 2 (purple) and a C-terminal region (blue). Ovastacin is replaced in this model by the closely related proteinase astacin (grey). The region of fetuin-B responsible for astacin inhibition is located in the transition from the first to the second domain (red), (modified according to Cuppari et al., IUCrJ, 2019).

Further Reading

Structure of mammalian plasma fetuin-B and its mechanism of selective metallopeptidase inhibition.

Cuppari A, Körschgen H, Fahrenkamp D, Schmitz C, Guevara T, Karmilin K, Kuske M, Olf M, Dietzel E, Yiallouros I, de Sanctis D, Goulas T, Weiskirchen R, Jahnen-Dechent W, Floehr J, Stoecker W, Jovine L, Gomis-Rüth.

FX.IUCrJ. 2019 Feb 28;6(Pt 2):317-330. doi: 10.1107/S2052252519001568. eCollection 2019 Mar 1. PMID: 30867929 

Fetuin-B, a liver-derived plasma protein is essential for fertilization.

Dietzel E, Wessling J, Floehr J, Schäfer C, Ensslen S, Denecke B, Rösing B, Neulen J, Veitinger T, Spehr M, Tropartz T, Tolba R, Renné T, Egert A, Schorle H, Gottenbusch Y, Hildebrand A, Yiallouros I, Stöcker W, Weiskirchen R, Jahnen-Dechent W.

Dev Cell. 2013 Apr 15;25(1):106-12. doi: 10.1016/j.devcel.2013.03.001. Epub 2013 Apr 4. PMID: 23562279