Organization of the archaeal MCM complex on DNA and implications for the helicase mechanism.
The homomultimeric archaeal mini-chromosome maintenance (MCM) complex serves as a simple model for the analogous heterohexameric eukaryotic complex. Here we investigate the organization and orientation of the MCM complex of the hyperthermophilic archaeon Sulfolobus solfataricus (Sso) on model DNA substrates. Sso MCM binds as a hexamer and slides on the end of a 3'-extended single-stranded DNA tail of a Y-shaped substrate; binding is oriented so that the motor domain of the protein faces duplex DNA. Two candidate beta-hairpin motifs within the MCM monomer have partially redundant roles in DNA binding. Notably, however, conserved basic residues within these motifs have nonequivalent roles in the helicase activity of MCM. On the basis of these findings, we propose a model for the mechanism of the helicase activity of MCM and note parallels with SV40 T antigen.
McGeoch
Adam T
AT
MRC Cancer Cell Unit, Hutchison MRC Research Centre, Hills Road, Cambridge, CB2 2XZ, UK.
Trakselis
Michael A
MA
Laskey
Ronald A
RA
Bell
Stephen D
SD
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D026341:Minichromosome Maintenance 1 Protein / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D012996:Solutions / Q000737:chemistry; D048229:Sulfolobus solfataricus / Q000737:chemistry
D019843:Archaeal Proteins; D004268:DNA-Binding Proteins; D026341:Minichromosome Maintenance 1 Protein; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D021122:Protein Subunits; D012996:Solutions; D004247:DNA; D000251:Adenosine Triphosphatases; D004265:DNA Helicases