title: A network of allosterically coupled residues in the bacteriophage T4 Mre11-Rad50 complex.
abstract: The Mre11-Rad50 (MR) protein complex, made up of a nuclease and ATPase, respectively, is involved in the processing of double-strand breaks as part of an intricate mechanism for their repair. Although it is clear that the MR complex is subject to allosteric regulation and that there is communication between the nuclease and ATPase active sites, the underlying mechanisms are poorly understood. We performed statistical coupling analysis on Mre11 and Rad50 to predict linked residues based on their evolutionary correlation. This analysis predicted a coevolving sector of six residues that may be allosterically coupled. The prediction was tested using double-mutant cycle analysis of nuclease and ATPase activity. The results indicate that a tyrosine residue located near the active site of Mre11 is allosterically coupled to several Rad50 residues located over 40 Å away. This allosteric coupling may be the basis for the reciprocal regulation of the ATPase and nuclease activities of the complex.
authors: Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, Iowa, 50011.
authors: Yang
authors: Y
authors: Gao
authors: Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, Iowa, 50011.
authors: Jennifer R
authors: JR
authors: Meyer
authors: Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, Iowa, 50011. swn@iastate.edu.
authors: Scott W
authors: SW
authors: Nelson
mesh_terms: D000494:Allosteric Regulation; D017122:Bacteriophage T4 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D014764:Viral Proteins
keywords: ATPase; MR complex; Mre11; Rad50; allostery; bacteriophage; double mutant cycle; gp46/47; nuclease; statistical coupling analysis