학술논문
Allosteric communication in DNA polymerase clamp loaders relies on a critical hydrogen-bonded junction.
Document Type
Academic Journal
Author
Subramanian S; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, United States.; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States.; Gorday K; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, United States.; Biophysics Graduate Group, University of California, Berkeley, Berkeley, United States.; Marcus K; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, United States.; Orellana MR; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, United States.; Ren P; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, United States.; Luo XR; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, United States.; O'Donnell ME; Howard Hughes Medical Institute, Rockefeller University, New York, United States.; Kuriyan J; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, United States.; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States.; Department of Chemistry, University of California, Berkeley, Berkeley, United States.; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, United States.
Source
Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
Subject
Language
English
Abstract
Clamp loaders are AAA+ ATPases that load sliding clamps onto DNA. We mapped the mutational sensitivity of the T4 bacteriophage sliding clamp and clamp loader by deep mutagenesis, and found that residues not involved in catalysis or binding display remarkable tolerance to mutation. An exception is a glutamine residue in the AAA+ module (Gln 118) that is not located at a catalytic or interfacial site. Gln 118 forms a hydrogen-bonded junction in a helical unit that we term the central coupler, because it connects the catalytic centers to DNA and the sliding clamp. A suppressor mutation indicates that hydrogen bonding in the junction is important, and molecular dynamics simulations reveal that it maintains rigidity in the central coupler. The glutamine-mediated junction is preserved in diverse AAA+ ATPases, suggesting that a connected network of hydrogen bonds that links ATP molecules is an essential aspect of allosteric communication in these proteins.
Competing Interests: SS, KG, KM, MO, PR, XL, MO No competing interests declared, JK Senior editor, eLife
(© 2021, Subramanian et al.)
Competing Interests: SS, KG, KM, MO, PR, XL, MO No competing interests declared, JK Senior editor, eLife
(© 2021, Subramanian et al.)