title: Transcriptional protein-protein cooperativity in POU/HMG/DNA complexes revealed by normal mode analysis.
abstract: Biomolecular cooperativity is of great scientific interest due to its role in biological processes. Two transcription factors (TFs), Oct-4 and Sox-2, are crucial in transcriptional regulation of embryonic stem cells. In this paper, we analyze how Oct-1 (a similar POU factor) and Sox-2, interact cooperatively at their enhancer binding sites in collective motions. Normal mode analysis (NMA) is implemented to study the collective motions of two complexes with each involving these TFs and an enhancer. The special structure of Oct proteins is analyzed comprehensively, after which each Oct/Sox group is reassembled into two protein pairs. We subsequently propose a segmentation idea to extract the most correlated segments in each pair, using correlations of motion magnitude curves. The median analysis on these correlation values shows the intimacy of subunit POUS (Oct-1) and Sox-2. Using those larger-than-median correlation values, we conduct statistical studies and propose several protein-protein cooperative modes (S and D) coupled with their subtypes. Additional filters are applied and similar results are obtained. A supplementary study on the rotation angle curves reaches an agreement with these modes. Overall, these proposed cooperative modes provide useful information for us to understand the complicated interaction mechanism in the POU/HMG/DNA complexes.
authors: Department of Electronic Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong.
authors: Debby D
authors: DD
authors: Wang
authors: Hong
authors: H
authors: Yan
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D050809:POU Domain Factors / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D006609:High Mobility Group Proteins; D046912:Multiprotein Complexes; D050809:POU Domain Factors; D014157:Transcription Factors; D004247:DNA