A Phosphomimetic Study Implicates Ser557 in Regulation of FOXP2 DNA Binding

The Protein Journal
Ashleigh BlaneSylvia Fanucchi

Abstract

FOXP2 is a transcription factor expressed in multiple tissues during embryonic development. FOXP2 regulates transcription by binding to DNA at its DNA binding domain, the forkhead domain (FHD) through the recognition helix. Ser557 is a residue located within the recognition helix that has the potential to become phosphorylated posttranslationally. In this study we investigated whether phosphorylation of Ser557 can influence the structure and DNA binding of the FOXP2 FHD. We did this by constructing S557E, a phosphomimetic mutant, and comparing its behaviour to the wild type. The mutation did not affect the secondary or tertiary structure of the protein although it did decrease the propensity of the FOXP2 FHD to form dimers. Most notably, the mutation showed significantly reduced DNA binding compared to the wild type as detected using electrophoretic mobility shift assays. Molecular docking was also performed in which the wild type, phosphomimetic mutant and phosphorylated wild-type were docked to DNA and their interactions with DNA were compared. These results indicated that the wild type forms more interactions with the DNA and that the phosphomimetic mutant as well as the phosphorylated wild type did not associate as favourab...Continue Reading

References

Nov 15, 1996·The Journal of Biological Chemistry·M HaoG Lozano
May 7, 1998·The International Journal of Biochemistry & Cell Biology·D S Latchman
May 7, 1998·The International Journal of Biochemistry & Cell Biology·S Akira
Jun 23, 1999·Proceedings of the National Academy of Sciences of the United States of America·W H BiggsK C Arden
Feb 13, 2002·Current Opinion in Structural Biology·Joy L Huffman, Richard G Brennan
Feb 13, 2003·Journal of the American Chemical Society·Cyril DominguezAlexandre M J J Bonvin
Apr 27, 2004·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Xiaohong GongDai Zhang
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Feb 17, 2005·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Tina L Tootle, Ilaria Rebay
Jul 20, 2005·Biochimica Et Biophysica Acta·Sharon M KellyNicholas C Price
Jan 13, 2006·Structure·James C StroudLin Chen
Aug 16, 2006·Cellular and Molecular Life Sciences : CMLS·J R Friedman, K H Kaestner
Apr 25, 2007·Nucleic Acids Research·Warren A Kibbe
Apr 25, 2007·Nucleic Acids Research·Ian W DavisDavid C Richardson
Aug 19, 2007·Nature Protocols·Lance M Hellman, Michael G Fried
Mar 11, 2009·Nature Reviews. Genetics·Sridhar Hannenhalli, Klaus H Kaestner
Mar 24, 2009·Trends in Genetics : TIG·Simon E Fisher, Constance Scharff
Mar 31, 2009·Trends in Cell Biology·Bérénice A Benayoun, Reiner A Veitia
Jun 6, 2009·Annual Review of Biochemistry·Mary Katherine Tarrant, Philip A Cole
Sep 10, 2009·The Journal of Biological Chemistry·Yi-Ju ChenPradip Raychaudhuri
Jan 29, 2010·Electrophoresis·Nina Y SidorovaDonald C Rau
Mar 25, 2010·Journal of Proteome Research·Panagiotis L Kastritis, Alexandre M J J Bonvin
Feb 22, 2011·Neuroscience Letters·Filip ŠpanielCyril Höschl
Jun 10, 2015·Biochemistry·Ashleigh Blane, Sylvia Fanucchi
Mar 8, 2016·Biochemistry·Gavin Morris, Sylvia Fanucchi

❮ Previous
Next ❯

Citations

Oct 13, 2020·Frontiers in Cell and Developmental Biology·Rocío Valle-BautistaAnayansi Molina-Hernández

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.