A conformational switch controls the DNA cleavage activity of λ integrase

Hideki Aihara, Hyock Joo Kwon, Simone E. Nunes-Düby, Arthur Landy, Tom Ellenberger

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The bacteriophage λ integrase protein (λ Int) belongs to a family of tyrosine recombinases that catalyze DNA rearrangements. We have determined a crystal structure of λ Int complexed with a cleaved DNA substrate through a covalent phosphotyrosine bond. In comparison to an earlier unliganded structure, we observe a drastic conformational change in DNA-bound λ Int that brings Tyr342 into the active site for cleavage of the DNA in cis. A flexible linker connects the central and the catalytic domains, allowing the protein to encircle the DNA. Binding specificity is achieved through direct interactions with the DNA and indirect readout of the flexibility of the att site. The conformational switch that activates λ Int for DNA cleavage exposes the C-terminal 8 residues for interactions with a neighboring Int molecule. The protein interactions mediated by λ Int's C-terminal tail offer a mechanism for the allosteric control of cleavage activity in higher order λ Int complexes.

Original languageEnglish (US)
Pages (from-to)187-198
Number of pages12
JournalMolecular Cell
Issue number1
StatePublished - Jul 1 2003

Bibliographical note

Funding Information:
We thank Christine Lank for technical assistance and members of the Landy and Ellenberger laboratories, especially Tapan Biswas, for their comments and suggestions. Thanks to Laura Silvian, Eric Toth, Brandt Eichman, John Genova, Shuchismita Dutta, and Tapan Biswas, as well as the staff of beamlines X-25 and X-12C at the National Synchrotron Light Source (Upton, NY) and station A1 and F1 at the Cornell High Energy Synchrotron Source (Ithaca, NY), for their assistance with the collection of X-ray diffraction data. This work was supported by National Institutes of Health grants GM33928 and GM62723 (awarded to A.L.), and grant GM59902 (awarded to T.E.), a fellowship from the Human Frontier Science Program (awarded to H.A.), and the resources of the Harvard-Armenise Structural Biology Center. T.E. is the Hsien Wu and Daisy Yen Wu Professor at Harvard Medical School.


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