Structural Insights of the Nucleotide-Dependent Conformational Changes of Thermotoga maritima MutL Using Small-Angle X-ray Scattering Analysis

MutL is required to assist the mismatch repair protein MutS during initiation of the methyl-directed mismatch repair (MMR) response in various organisms ranging from prokaryotes to eukaryotes. Despite this necessity, the inherent propensity of MutL to aggregate has led to significant difficulties in...

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Published in:Journal of biochemistry (Tokyo) 2009-02, Vol.145 (2), p.199-206
Main Authors: Kim, Tae Gyun, Cha, Hyung Jin, Lee, Hyung Ju, Heo, Seong-Dal, Choi, Kwan Yong, Ku, Ja Kang, Ban, Changill
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases - chemistry
Amino Acid Sequence
Bacterial Proteins - chemistry
Binding Sites
Chromatography, Gel
conformational change
Dimerization
DNA Mismatch Repair
DNA, Single-Stranded - chemistry
DNA, Single-Stranded - metabolism
Escherichia coli MutL
Escherichia coli Proteins - chemistry
Methyl-directed mismatch repair
Models, Molecular
Molecular Sequence Data
MutL Proteins
Nucleotides - metabolism
Protein Conformation
Sequence Alignment
Small-angle X-ray scattering
Thermotoga maritima - metabolism
Thermotoga maritima MSB8 MutL
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Summary:MutL is required to assist the mismatch repair protein MutS during initiation of the methyl-directed mismatch repair (MMR) response in various organisms ranging from prokaryotes to eukaryotes. Despite this necessity, the inherent propensity of MutL to aggregate has led to significant difficulties in determining its biological relationship with other MMR-related proteins. Here, we perform analysis on the thermostable MutL protein found in Thermotoga maritima MSB8 (TmL). Size exclusion chromatographic analysis indicates the lack of aggregated forms with the exception of a dimeric TmL. Small-angle X-ray scattering (SAXS) analysis reveals that the solution structures of the full-length TmL and its corresponding complexes with nucleotides and ssDNA undergo conformational changes. The elucidated TmL SAXS model is superimposed to the crystal structure of the C-terminal domain of Escherichia coli MutL. In addition, the N-terminal SAXS model of TmL exists as monomeric form, indicating that TmL has a structurally flexible N-terminal domain. TmL SAXS analysis can suggest a considerable possibility on a new 3D view of the previously unresolved full-length MutL molecule.
ISSN:0021-924X
1756-2651
DOI:10.1093/jb/mvn157