4JND

Structure of a C.elegans sex determining protein

Summary for 4JND

• Entry DOI: 10.2210/pdb4jnd/pdb
• Descriptor: Ca(2+)/calmodulin-dependent protein kinase phosphatase, MAGNESIUM ION (3 entities in total)
• Functional Keywords: novel fold, sex determination, cytosol, male promoting, hydrolase
• Biological source: Caenorhabditis elegans (nematode)
• Total number of polymer chains: 1
• Total formula weight: 51419.84

Authors

Feng, Y.,Zhang, Y.,Ge, J.,Yang, M. (deposition date: 2013-03-15, release date: 2013-06-19, Last modification date: 2024-03-20)

Primary citation

Zhang, Y.,Zhao, H.,Wang, J.,Ge, J.,Li, Y.,Gu, J.,Li, P.,Feng, Y.,Yang, M.
Structural insight into Caenorhabditis elegans sex-determining protein FEM-2.
J.Biol.Chem., 288:22058-22066, 2013

PubMed Abstract: 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.

PubMed: 23760267
DOI: 10.1074/jbc.M113.464339

Experimental method

X-RAY DIFFRACTION (1.652 Å)