4jnd

Publication Abstract from PubMed

In the nematode Caenorhabditis elegans, fem-1, fem-2, and fem-3 play crucial roles in male sexual development. Among these three genes, fem-2 encodes a PP2C (serine/threonine phosphatase type 2C)-like protein, whose activity promotes the development of masculinity. Different from the canonical PP2Cs, FEM-2 consists of an additional N-terminal domain (NTD) apart from its C-terminal catalytic domain. Interestingly, genetic studies have indicated indispensable roles for both of these two domains of FEM-2 in promoting male development, but the underlying mechanism remains unknown. In the present study, we solved the crystal structure of full-length FEM-2, which revealed a novel structural fold formed by its NTD. Structural and functional analyses demonstrated that the NTD did not directly regulate the in vitro dephosphorylation activity of FEM-2, but instead functioned as a scaffold domain in the assembly of the FEM-1/2/3 complex, the executioner in the final step of the sex determination pathway. Biochemical studies further identified the regions in the NTD involved in FEM-1 and FEM-3 interactions. Our results not only identified a novel fold formed by the extra domain of a noncanonical PP2C enzyme, but also provided important insights into the molecular mechanism of how the NTD works in mediating the sex-determining role of FEM-1/2/3 complex.

Structural insight into Caenorhabditis elegans sex-determining protein FEM-2.,Zhang Y, Zhao H, Wang J, Ge J, Li Y, Gu J, Li P, Feng Y, Yang M J Biol Chem. 2013 Jul 26;288(30):22058-66. doi: 10.1074/jbc.M113.464339. Epub, 2013 Jun 11. PMID:23760267^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.