Structural basis for suppression of hypernegative DNA supercoiling by E. coli topoisomerase I.
Escherichia coli topoisomerase I has an essential function in preventing hypernegative supercoiling of DNA. A full length structure of E. coli topoisomerase I reported here shows how the C-terminal domains bind single-stranded DNA (ssDNA) to recognize the accumulation of negative supercoils in duplex DNA. These C-terminal domains of E. coli topoisomerase I are known to interact with RNA polymerase, and two flexible linkers within the C-terminal domains may assist in the movement of the ssDNA for the rapid removal of transcription driven negative supercoils. The structure has also unveiled for the first time how the 4-Cys zinc ribbon domain and zinc ribbon-like domain bind ssDNA with primarily π-stacking interactions. This novel structure, in combination with new biochemical data, provides important insights into the mechanism of genome regulation by type IA topoisomerases that is essential for life, as well as the structures of homologous type IA TOP3α and TOP3β from higher eukaryotes that also have multiple 4-Cys zinc ribbon domains required for their physiological functions.
Structural Biology Center, Biosciences, Argonne National Laboratory, 9700 S. Cass Avenue, Argonne, IL 60439, USA ktan@anl.gov.
Kemin
K
Tan
Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8 St, Miami, FL 33199, USA.
Qingxuan
Q
Zhou
Department of Biochemistry and Molecular Biology, Basic Science Building, New York Medical College, Valhalla, NY 10595, USA.
Bokun
B
Cheng
Department of Biochemistry and Molecular Biology, Basic Science Building, New York Medical College, Valhalla, NY 10595, USA.
Zhongtao
Z
Zhang
Structural Biology Center, Biosciences, Argonne National Laboratory, 9700 S. Cass Avenue, Argonne, IL 60439, USA.
Andrzej
A
Joachimiak
Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8 St, Miami, FL 33199, USA Biomolecular Sciences Institute, Florida International University, 11200 SW 8 St, Miami, FL 33199, USA ytsedinh@fiu.edu.
Yuk-Ching
YC
Tse-Dinh
D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000737:chemistry* / Q000378:metabolism; D004278:DNA, Superhelical / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D004277:DNA, Single-Stranded; D004278:DNA, Superhelical; D029968:Escherichia coli Proteins; D004264:DNA Topoisomerases, Type I