PMID:15470502
| Citation |
Guarné, A, Ramon-Maiques, S, Wolff, EM, Ghirlando, R, Hu, X, Miller, JH and Yang, W (2004) Structure of the MutL C-terminal domain: a model of intact MutL and its roles in mismatch repair. EMBO J. 23:4134-45 |
|---|---|
| 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. |
| Links |
PubMed PMC524388 Online version:10.1038/sj.emboj.7600412 |
| Keywords |
Adenosine Triphosphatases/chemistry; Adenosine Triphosphatases/genetics; Adenosine Triphosphatases/metabolism; Amino Acid Sequence; Base Pair Mismatch; Crystallography, X-Ray; DNA/metabolism; DNA Helicases/metabolism; DNA Repair; Dimerization; Enzyme Activation; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Humans; Models, Molecular; Molecular Sequence Data; Mutation; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Alignment |
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