title: Structural insights of the nucleotide-dependent conformational changes of Thermotoga maritima MutL using small-angle X-ray scattering analysis.
abstract: 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.
authors.affiliation: Department of Chemistry, Pohang University of Science and Technology, Pohang, Gyungbuk 790-784, Korea.
authors.forename: Tae Gyun
authors.initials: TG
authors.lastname: Kim
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Cha
authors.forename: Hyung Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Seong-Dal
authors.initials: SD
authors.lastname: Heo
authors.forename: Kwan Yong
authors.initials: KY
authors.lastname: Choi
authors.forename: Ja Kang
authors.initials: JK
authors.lastname: Ku
authors.forename: Changill
authors.initials: C
authors.lastname: Ban
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D002850:Chromatography, Gel; D053843:DNA Mismatch Repair; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D029968:Escherichia coli Proteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000070956:MutL Proteins; D009711:Nucleotides / Q000378:metabolism*; D011487:Protein Conformation; D016415:Sequence Alignment; D020124:Thermotoga maritima / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004277:DNA, Single-Stranded; D029968:Escherichia coli Proteins; C074770:MutL protein, E coli; D009711:Nucleotides; D000251:Adenosine Triphosphatases; D000070956:MutL Proteins