Structure of the MutL C-terminal domain: a model of intact MutL and its roles in mismatch repair Academic Article uri icon

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abstract

  • MutL assists the mismatch recognition protein MutS to initiate and coordinate mismatch repair in species ranging from bacteria to humans. The MutL N-terminal ATPase domain is highly conserved, but the C-terminal region shares little sequence similarity among MutL homologs. We report here the crystal structure of the Escherichia coli MutL C-terminal dimerization domain and the likelihood of its conservation among MutL homologs. A 100-residue proline-rich linker between the ATPase and dimerization domains, which generates a large central cavity in MutL dimers, tolerates sequence substitutions and deletions of one-third of its length with no functional consequences in vivo or in vitro. Along the surface of the central cavity, residues essential for DNA binding are located in both the N- and C-terminal domains. Each domain of MutL interacts with UvrD helicase and is required for activating the helicase activity. The DNA-binding capacity of MutL is correlated with the level of UvrD activation. A model of how MutL utilizes its ATPase and DNA-binding activities to mediate mismatch-dependent activation of MutH endonuclease and UvrD helicase is proposed.

authors

  • Guarne, Alba
  • Guarné, Alba
  • Ramon-Maiques, Santiago
  • Wolff, Erika M
  • Ghirlando, Rodolfo
  • Hu, Xiaojian
  • Miller, Jeffrey H
  • Yang, Wei

publication date

  • October 27, 2004

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