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Solution structure and backbone dynamics of the DNA‐binding domain of FOXP1: Insight into its domain swapping and DNA binding
Author(s) -
Chu YuanPing,
Chang ChiaHao,
Shiu JiaHau,
Chang YaoTsung,
Chen ChiuYueh,
Chuang WoeiJer
Publication year - 2011
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.626
Subject(s) - dimer , chemistry , mutant , dna , monomer , crystallography , dna binding domain , biophysics , stereochemistry , transcription factor , biochemistry , biology , gene , polymer , organic chemistry
FOXP1 belongs to the P‐subfamily of forkhead transcription factors and contains a conserved forkhead DNA‐binding domain. According to size exclusion chromatography analysis, the forkhead domain of FOXP1 existed as a mixture of monomer and dimer. The dissociation constants of the forkhead domain of wild‐type, C61S, and C61Y mutants of FOXP1 were 27.3, 28.8, and 332.0 μM, respectively. In contrast, FOXP1 A39P mutant formed only a monomer. NMR analysis also showed that FOXP1 C61S and C61Y mutants existed as a mixture. The solution structure of FOXP1 A39P/C61Y mutant was similar to the X‐ray structure of the FOXP2 monomer. Comparison of backbone dynamics of FOXP1 A39P/C61Y and C61Y mutants showed that the residues preceding helix 3, the hinge region, exhibited the largest conformational exchange in FOXP1 monomer. The A39 residue of FOXP1 dimer has a lower order parameter with internal motion on the ps‐ns timescale, suggesting that the dynamics of the hinge region of FOXP1 are important in the formation of the swapped dimer. The analysis also showed that the residues exhibiting the motions on the ps‐ns and μs‐ms timescales were located at the DNA‐binding surface of FOXP1, suggesting the interactions between FOXP1 and DNA may be highly dynamic.