Multiple interfaces between a serine recombinase and an enhancer control site-specific DNA inversion
Meghan M McLean,
Yong Chang,
Gautam Dhar,
John K Heiss,
Reid C Johnson
Affiliations
Meghan M McLean
Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
Yong Chang
Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
Gautam Dhar
Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
John K Heiss
Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
Reid C Johnson
Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States
Serine recombinases are often tightly controlled by elaborate, topologically-defined, nucleoprotein complexes. Hin is a member of the DNA invertase subclass of serine recombinases that are regulated by a remote recombinational enhancer element containing two binding sites for the protein Fis. Two Hin dimers bound to specific recombination sites associate with the Fis-bound enhancer by DNA looping where they are remodeled into a synaptic tetramer competent for DNA chemistry and exchange. Here we show that the flexible beta-hairpin arms of the Fis dimers contact the DNA binding domain of one subunit of each Hin dimer. These contacts sandwich the Hin dimers to promote remodeling into the tetramer. A basic region on the Hin catalytic domain then contacts enhancer DNA to complete assembly of the active Hin tetramer. Our results reveal how the enhancer generates the recombination complex that specifies DNA inversion and regulates DNA exchange by the subunit rotation mechanism.
