Structure of the bacteriophage Mu transposase core: a common structural motif for DNA transposition and retroviral

P Rice1, K Mizuuchi

  • 1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0540, USA.

Cell
|July 28, 1995
PubMed

Insights

The crystal structure of bacteriophage Mu transposase (MuA) reveals a similarity to HIV-1 integrase. Its active site appears inactive in monomeric form, suggesting DNA binding activates MuA.

Area of Science:

  • Structural Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Bacteriophage Mu transposase (MuA) is essential for viral DNA integration.
  • Understanding MuA's structure is key to elucidating its catalytic mechanism.
  • MuA shares functional similarities with other DNA-processing enzymes like HIV-1 integrase.

Purpose of the Study:

  • To determine the high-resolution crystal structure of the MuA core domain.
  • To compare the structural features of MuA with related enzymes.
  • To investigate the structural basis for MuA's regulation and activation.

Main Methods:

  • X-ray crystallography at 2.4 A resolution.
  • Analysis of three independent monomer structures from two crystal forms.
  • Comparative structural analysis with other nucleases.

Main Results:

  • The crystal structure of the MuA core domain was elucidated.
  • MuA's active site subdomain shows significant structural similarity to HIV-1 integrase.
  • The active site was consistently observed in an apparently inactive conformation in the monomer.
  • A beta-barrel subdomain connects to the active site subdomain.

Conclusions:

  • MuA's structure shares conserved features with other integrases, suggesting a common evolutionary origin or functional adaptation.
  • The inactive conformation of the active site in the monomer implies a regulatory mechanism.
  • Interactions between subdomains may control MuA activity, potentially linking DNA binding to activation.

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