A Single Amino Acid in the Hinge Loop Region of the FOXP Forkhead Domain is Significant for Dimerisation

The Protein Journal
Kershia PerumalSylvia Fanucchi

Abstract

The forkhead box (FOX) proteins are a family of transcription factors that interact with DNA via a winged helix motif that forms part of the forkhead domain. The FOXP (FOXP1-4) subfamily is unique in the family in that the forkhead domains of these proteins are able to dimerise via domain swapping. In this event, structural elements are exchanged via extension of the hinge loop region. Despite the high sequence homology among the FOXP subfamily members, the stability of their forkhead domain dimers varies, with FOXP3 forming the most stable dimer. An amino acid difference is observed in the hinge region of the FOXP subfamily where a tyrosine in all members is replaced with a phenylalanine in FOXP3. In this work, the role of phenylalanine at this position in the hinge region was investigated. This was done by creating the Y540F variant of the FOXP2 forkhead domain. The effect of the Y540F mutation on the structure, dimerisation propensity and DNA binding ability of the FOXP subfamily was investigated. The mutation altered the structure of the protein by decreasing the disorder of the backbone as measured by circular dichroism spectroscopy and by altering the local environment of the hinge region as measured by tryptophan fluores...Continue Reading

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Citations

Mar 8, 2016·Biochemistry·Gavin Morris, Sylvia Fanucchi
Mar 27, 2016·Journal of Molecular Biology·Dong-Sun LeeSudha Veeraraghavan
May 6, 2016·International Journal of Molecular Sciences·Yann GambinEmma Sierecki
Jul 25, 2017·Journal of Medical Genetics·Ilse MeerschautBert Callewaert
May 31, 2018·The Protein Journal·Ashleigh BlaneSylvia Fanucchi
Oct 29, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Lot Snijders BlokSimon E Fisher

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