Mutations in subdomain B of the minichromosome maintenance (MCM) helicase affect DNA binding and modulate conformational transitions.

The Journal of Biological Chemistry
Elizabeth R JenkinsonJames Chong

Abstract

Minichromosome maintenance (MCM) proteins are believed to provide the replicative helicase activity in eukaryotes and archaea. The single MCM orthologue from Methanothermobacter thermautotrophicus (MthMCM) has been extensively characterized as a model of the eukaryotic heterohexameric MCM complex. MthMCM forms high molecular weight complexes in solution consistent with a dodecamer. Visualization of this complex by electron microscopy suggests that single and double heptameric or hexameric rings can form. We have mutated two arginine residues (Arg-137, Arg-160) in the N-terminal subdomain B of MthMCM based on their apparent potential to form inter-ring hydrogen bonds. Both the single R137A and the double R137A,R160A mutants were characterized by a combination of biophysical, biochemical, and electron microscopy techniques. Biophysical analysis coupled with electron microscopy studies shows that the R137A mutant forms a double heptameric ring, whereas the R137A,R160A protein assembles as a single heptamer. They both show a defect in DNA binding and a concomitant conformational change in subdomain A, with the double mutant displaying significant defects in helicase activity as well. We propose a model in which MCM loading and the ...Continue Reading

References

Dec 23, 1988·Nucleic Acids Research·J LisziewiczH Küntzel
Jan 1, 1996·Journal of Structural Biology·M van HeelM Schatz
Dec 6, 1996·Science·B Stillman
May 27, 1997·Proceedings of the National Academy of Sciences of the United States of America·S DonovanJ F Diffley
Jun 27, 1997·Cell·D R Edgell, W F Doolittle
Sep 26, 1997·The Journal of Biological Chemistry·Y Ishimi
Jan 1, 1997·Annual Review of Cell and Developmental Biology·A Dutta, S P Bell
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·Z KelmanJ Hurwitz
Jan 25, 2000·The Journal of Biological Chemistry·T A Prokhorova, J J Blow
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·J P ChongB Stillman
Mar 16, 2000·Proceedings of the National Academy of Sciences of the United States of America·B K Tye
Jan 28, 2003·Nature Structural Biology·Ryan J FletcherXiaojiang S Chen
Aug 9, 2003·Nucleic Acids Research·Ian GraingeDale B Wigley
Oct 21, 2003·EMBO Reports·Tillmann PapeSilvia Onesti
Jan 18, 2005·Nucleic Acids Research·Jae-Ho ShinZvi Kelman
Jan 27, 2005·Journal of Molecular Biology·Yen-Ju ChenEdward H Egelman
Jun 2, 2005·Nature Reviews. Molecular Cell Biology·J Julian Blow, Anindya Dutta
Aug 24, 2005·Nature Structural & Molecular Biology·Adam T McGeochStephen D Bell
Sep 6, 2005·Nature Structural & Molecular Biology·James P J Chong
Oct 14, 2005·The Journal of Biological Chemistry·Ryan J FletcherXiaojiang S Chen
May 9, 2006·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth R Jenkinson, James P J Chong
May 30, 2006·Journal of Structural Biology·Alessandro CostaSilvia Onesti
Jun 27, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stephen E MoyerMichael R Botchan
Aug 9, 2006·Nucleic Acids Research·Sandrine CastellaCyril M Sanders
Oct 26, 2006·Nucleic Acids Research·Alessandro CostaSilvia Onesti
Jan 11, 2008·Nucleic Acids Research·Nozomi SakakibaraZvi Kelman
Mar 21, 2008·Journal of Molecular Biology·Alessandro Costa, Ardan Patwardhan
Jul 25, 2008·The EMBO Journal·Alessandro CostaSilvia Onesti
Nov 13, 2008·The Journal of Biological Chemistry·Jae-Ho ShinZvi Kelman

❮ Previous
Next ❯

Citations

Oct 11, 2011·Nucleic Acids Research·June Sanchez-BerrondoGuillermo Montoya
Feb 16, 2013·Chromosoma·Silvia Onesti, Stuart A MacNeill
Jan 1, 2014·Journal of Molecular Biology·Yang FuXiaojiang S Chen
Nov 6, 2015·Archaea : an International Microbiological Journal·Justin M Miller, Eric J Enemark
May 6, 2009·Molecular Microbiology·Nozomi SakakibaraZvi Kelman
Sep 29, 2009·Critical Reviews in Biochemistry and Molecular Biology·Alessandro Costa, Silvia Onesti

❮ Previous
Next ❯

Related Concepts

Related Feeds

Archaeogenetics

Recent advances in genomic sequencing has led to the discovery of new strains of Archaea and shed light on their evolutionary history. Discover the latest research on Archaeogenetics here.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.