title: Localized frustration and binding-induced conformational change in recognition of 5S RNA by TFIIIA zinc finger.
abstract: Protein TFIIIA is composed of nine tandemly arranged Cys2His2 zinc fingers. It can bind either to the 5S RNA gene as a transcription factor or to the 5S RNA transcript as a chaperone. Although structural and biochemical data provided valuable information on the recognition between the TFIIIIA and the 5S DNA/RNA, the involved conformational motions and energetic factors contributing to the binding affinity and specificity remain unclear. In this work, we conducted MD simulations and MM/GBSA calculations to investigate the binding-induced conformational changes in the recognition of the 5S RNA by the central three zinc fingers of TFIIIA and the energetic factors that influence the binding affinity and specificity at an atomistic level. Our results revealed drastic interdomain conformational changes between these three zinc fingers, involving the exposure/burial of several crucial DNA/RNA binding residues, which can be related to the competition between DNA and RNA for the binding of TFIIIA. We also showed that the specific recognition between finger 4/finger 6 and the 5S RNA introduces frustrations to the nonspecific interactions between finger 5 and the 5S RNA, which may be important to achieve optimal binding affinity and specificity.
authors.affiliation: National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University , Nanjing, Jiangsu 210093, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Tan
authors.forename: Wenfei
authors.initials: W
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D012341:RNA, Ribosomal, 5S / Q000737:chemistry*; D035582:Transcription Factor TFIIIA / Q000737:chemistry*; D016335:Zinc Fingers
chemical_list: D012341:RNA, Ribosomal, 5S; D035582:Transcription Factor TFIIIA