6akp | pdb_00006akp
Crystal Structural of FOXC2 DNA binding domain bound to PC promoter
Structural highlights
Disease[FOXC2_HUMAN] Defects in FOXC2 are the cause of lymphedema hereditary type 2 (LMPH2) [MIM:153200]; also known as Meige lymphedema. Hereditary lymphedema is a chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections, and physical impairment.[1] Defects in FOXC2 are a cause of lymphedema-yellow nails (LYYN) [MIM:153300]. LYYN is characterized by yellow, dystrophic, thick and slowly growing nails, associated with lymphedema and respiratory involvement. Lymphedema occurs more often in the lower limbs. It can appear at birth or later in life. Onset generally follows the onset of ungual abnormalities. Defects in FOXC2 are a cause of lymphedema-distichiasis (LYD) [MIM:153400]. LYD is characterized by primary limb lymphedema usually starting at puberty (but in some cases later or at birth) and associated with distichiasis (double rows of eyelashes, with extra eyelashes growing from the Meibomian gland orifices).[2] Function[FOXC2_HUMAN] Transcriptional activator. Might be involved in the formation of special mesenchymal tissues.[3] Publication Abstract from PubMedThe FOXC family of transcription factors (FOXC1 and FOXC2) plays essential roles in the regulation of embryonic, ocular, and cardiac development. Mutations and abnormal expression of FOXC proteins are implicated in genetic diseases as well as cancer. In this study, we determined two crystal structures of the DNA-binding domain (DBD) of human FOXC2 protein, in complex with different DNA sites. The FOXC2-DBD adopts the winged-helix fold with helix H3 contributing to all the base specific contacts, while the N-terminus, wing 1, and the C-terminus of FOXC2-DBD all make additional contacts with the phosphate groups of DNA. Our structural, biochemical, and bioinformatics analyses allow us to revise the previously proposed DNA recognition mechanism and provide a model of DNA binding for the FOXC proteins. In addition, our structural analysis and accompanying biochemical assays provide a molecular basis for understanding disease-causing mutations in FOXC1 and FOXC2. Structural basis for DNA recognition by FOXC2.,Chen X, Wei H, Li J, Liang X, Dai S, Jiang L, Guo M, Qu L, Chen Z, Chen L, Chen Y Nucleic Acids Res. 2019 Feb 5. pii: 5306577. doi: 10.1093/nar/gkz077. PMID:30722065[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
