4I1L

Structural and Biological Features of FOXP3 Dimerization Relevant to Regulatory T Cell Function

Summary for 4I1L

• Entry DOI: 10.2210/pdb4i1l/pdb
• Related: 3HSX
• Descriptor: Forkhead box protein P3, SULFATE ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: foxp3, dimerization, complex ensemble, stability, regulatory activity, acetyation, dna-binding, metal-binding, nucleus, transcription, zinc-finger, transcription regulator
• Biological source: Mus musculus (mouse)
• Cellular location: Nucleus (Potential): Q99JB6
• Total number of polymer chains: 1
• Total formula weight: 10758.09

Authors

Song, X.M.,Greene, M.I.,Zhou, Z.C. (deposition date: 2012-11-21, release date: 2012-12-05, Last modification date: 2024-03-20)

Primary citation

Song, X.,Li, B.,Xiao, Y.,Chen, C.,Wang, Q.,Liu, Y.,Berezov, A.,Xu, C.,Gao, Y.,Li, Z.,Wu, S.L.,Cai, Z.,Zhang, H.,Karger, B.L.,Hancock, W.W.,Wells, A.D.,Zhou, Z.,Greene, M.I.
Structural and biological features of FOXP3 dimerization relevant to regulatory T cell function.
Cell Rep, 1:665-675, 2012

PubMed Abstract: FOXP3 is a key transcription factor for regulatory T cell function. We report the crystal structure of the FOXP3 coiled-coil domain, through which a loose or transient dimeric association is formed and modulated, accounting for the activity variations introduced by disease-causing mutations or posttranslational modifications. Structure-guided mutagenesis revealed that FOXP3 coiled-coil-mediated homodimerization is essential for Treg function in vitro and in vivo. In particular, we identified human FOXP3 K250 and K252 as key residues for the conformational change and stability of the FOXP3 dimer, which can be regulated by protein posttranslational modifications such as reversible lysine acetylation. These studies provide structural and mechanistic explanations for certain disease-causing mutations in the coiled-coil domain of FOXP3 that are commonly found in IPEX syndrome. Overall, the regulatory machinery involving homooligomerization, acetylation, and heteroassociation has been dissected, defining atomic insights into the biological and pathological characteristics of the FOXP3 complex.

PubMed: 22813742
DOI: 10.1016/j.celrep.2012.04.012

Experimental method

X-RAY DIFFRACTION (2.1 Å)