Crystal structure of Mycobacterium tuberculosis O6-methylguanine-DNA methyltransferase protein clusters assembled on to damaged DNA
| Autor: | Maria Ciaramella, Franca Rossi, Samarpita Lahiri, Mario Serpe, Giuseppe Perugino, Silvia Garavaglia, Dominik Rejman, Radek Pohl, Riccardo Miggiano, Ondřej Páv, Menico Rizzi |
|---|---|
| Přispěvatelé: | Miggiano, Riccardo, Perugino, Giuseppe, Ciaramella, Maria, Serpe, Mario, Rejman, Dominik, Páv, Ondřej, Pohl, Radek, Garavaglia, Silvia, Lahiri, Samarpita, Rizzi, Menico, Rossi, Franca |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
crystal structure DNA damage Guanine DNA repair O6-methylguanine-DNA methyltransferase Bacterial Protein DNA-binding protein Mycobacterium tuberculosi Biology medicine.disease_cause Biochemistry DNA methyltransferase Protein Structure Secondary law.invention 03 medical and health sciences chemistry.chemical_compound O(6)-Methylguanine-DNA Methyltransferase Bacterial Proteins law medicine Point Mutation Molecular Biology Mutation Crystallography O-6-methylguanine-DNA methyltransferase Cell Biology Mycobacterium tuberculosis Protein Structure Tertiary 030104 developmental biology chemistry Recombinant DNA co-operativity DNA DNA Damage |
| Zdroj: | Europe PubMed Central Biochemical journal (Lond., 1984) 473 (2016). doi:10.1042/BJ20150833 info:cnr-pdr/source/autori:Miggiano R, Perugino G, Ciaramella M, Serpe M, Rejman D, Páv O, Pohl R, Garavaglia S, Lahiri S, Rizzi M, Rossi F/titolo:Crystal structure of Mycobacterium tuberculosis O6-methylguanine-DNA methyltransferase protein clusters assembled onto damaged DNA./doi:10.1042%2FBJ20150833/rivista:Biochemical journal (Lond., 1984)/anno:2016/pagina_da:/pagina_a:/intervallo_pagine:/volume:473 |
| DOI: | 10.1042/BJ20150833 |
| Popis: | Mycobacterium tuberculosis O 6-methylguanine-DNA methyltransferase (MtOGT) contributes to protect the bacterial GC-rich genome against the pro-mutagenic potential of O6-methylated guanine in DNA. Several strains of M. tuberculosis found worldwide encode a point-mutated O6-methylguanine-DNA methyltransferase (OGT) variant (MtOGT-R37L), which displays an arginine-to-leucine substitution at position 37 of the poorly functionally characterized N-terminal domain of the protein. Although the impact of this mutation on the MtOGT activity has not yet been proved in vivo, we previously demonstrated that a recombinant MtOGT-R37L variant performs a suboptimal alkylated-DNA repair in vitro, suggesting a direct role for the Arg37-bearing region in catalysis. The crystal structure of MtOGT complexed with modified DNA solved in the present study reveals details of the protein–protein and protein–DNA interactions occurring during alkylated-DNA binding, and the protein capability also to host unmodified bases inside the active site, in a fully extrahelical conformation. Our data provide the first experimental picture at the atomic level of a possible mode of assembling three adjacent MtOGT monomers on the same monoalkylated dsDNA molecule, and disclose the conformational flexibility of discrete regions of MtOGT, including the Arg37-bearing random coil. This peculiar structural plasticity of MtOGT could be instrumental to proper protein clustering at damaged DNA sites, as well as to protein–DNA complexes disassembling on repair. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|