Molecular Dynamics Simulations of Ternary Complexes: Comparisons of LEAFY Protein Binding to Different DNA Motifs.
LEAFY (LFY) is a plant-specific transcription factor, with a variety of roles in different species. LFY contains a conserved DNA-binding domain (DBD) that determines its DNA-binding specificity. Recently, the structures of the dimeric LFY-DBD bound to different DNA motifs were successively solved by X-ray crystallography. In this article, molecular dynamics (MD) simulations are employed to study two crystal structures of DNA-bound LFY protein from angiosperms and the moss Physcomitrella patens, respectively. The comparison of stabilities of the two systems is consistent with the experimental data of binding affinities. The calculation of hydrogen bonds showed that position 312 in LFY determines the difference of DNA-binding specificity. By using principal component analysis (PCA) and free energy landscape (FEL) methods, the open-close conformational change of the dimerization interface was found to be important for the system stability. At the dimerization interface, the protein-protein interaction has multiple influences on the cooperative DNA binding of LFY. The following analysis of DNA structural parameters further revealed that the protein-protein interaction contributes varying roles according to the specific DNA-binding efficiency. We propose that the protein-protein interaction serves a dual function as a connector between LFY monomers and a regulator of DNA-binding specificity. It will improve the robustness and adaptivity of the LFY-DNA ternary structure. This study provides some new insights into the understanding of the dynamics and interaction mechanism of dimeric LFY-DBD bound to DNA at the atomic level.
†College of Informatics, South China Agricultural University, Guangzhou 510642, China.
Hua
H
Wan
‡Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou 213001, China.
Shan
S
Chang
§Faculty of Biotechnology Industry, Chengdu University, Chengdu 610106, China.
Jian-ping
JP
Hu
∥School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Yuan-xin
YX
Tian
†College of Informatics, South China Agricultural University, Guangzhou 510642, China.
Xu-hong
XH
Tian
D017360:Arabidopsis; D029681:Arabidopsis Proteins / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D019068:Bryopsida; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D009068:Movement; D059372:Nucleotide Motifs; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D013816:Thermodynamics; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D029681:Arabidopsis Proteins; C074747:LFY protein, Arabidopsis; D014157:Transcription Factors; D004247:DNA