4jnd
Structure of a C.elegans sex determining proteinStructure of a C.elegans sex determining protein
Structural highlights
Function[FEM2_CAEEL] Probable phosphatase involved in the regulation of sex determination. Plays an important role in regulating a pathway transducing a non-cell-autonomous signal to a nuclear transcription factor. Promotes apoptosis. Together with fem-3 associates with the CBC(fem-1) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of tra-1. Publication Abstract from PubMedIn 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. References
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