A structural basis for allosteric control of DNA recombination by lambda integrase.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE

Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.

Bacteriophage lambda/*enzymology ; DNA, Cruciform/*chemistry ; DNA, Cruciform/*metabolism ; Integrases/*chemistry ; Integrases/*metabolism ; Recombination, Genetic/*genetics; Allosteric Regulation ; Attachment Sites, Microbiological/genetics ; Base Sequence ; Catalysis ; Crystallography, X-Ray ; DNA, Cruciform/genetics ; Isomerism ; Models, Molecular ; Nucleic Acid Conformation ; Pliability ; Protein Conformation ; Structure-Activity Relationship

Site-specific DNA recombination is important for basic cellular functions including viral integration, control of gene expression, production of genetic diversity and segregation of newly replicated chromosomes, and is used by bacteriophage lambda to integrate or excise its genome into and out of the host chromosome. lambda recombination is carried out by the bacteriophage-encoded integrase protein (lambda-int) together with accessory DNA sites and associated bending proteins that allow regulation in response to cell physiology. Here we report the crystal structures of lambda-int in higher-order complexes with substrates and regulatory DNAs representing different intermediates along the reaction pathway. The structures show how the simultaneous binding of two separate domains of lambda-int to DNA facilitates synapsis and can specify the order of DNA strand cleavage and exchange. An intertwined layer of amino-terminal domains bound to accessory (arm) DNAs shapes the recombination complex in a way that suggests how arm binding shifts the reaction equilibrium in favour of recombinant products.

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R01 GM033928 United States GM NIGMS NIH HHS; R01 GM062723 United States GM NIGMS NIH HHS

PDB 1Z19; 1Z1G; Z1B

0 (DNA, Cruciform)
EC 2.7.7.- (Integrases)

Date Created: 20050624 Date Completed: 20050714 Latest Revision: 20181227

20240829

PMC1809751

10.1038/nature03657

15973401