Biological functions of the WAP domain-containing multidomain proteins WFIKKN1 and WFIKKN2

Abstract

WFIKKN1 and WFIKKN2 are two closely related multidomain proteins consisting of a WAP (whey acidic protein)-, a follistatin-, an immunoglobulin-, two Kunitz-type protease inhibitor-domains and an NTR domain (netrin domain). Recent experiments have shown that both WFIKKN1 and WFIKKN2 bind myostatin and GDF11 (growth and differentiation factor 11) with high affinity and are potent antagonists of these growth factors. Structure–function studies on WFIKKN proteins have revealed that their interactions with GDF8 and GDF11 are mediated primarily by the follistatin and NTR domains.