Solution structure of the helicase-interaction domain of the primase DnaG: a model for helicase activation.
The helicase-primase interaction is a critical event in DNA replication and is mediated by a putative helicase-interaction domain within the primase. The solution structure of the helicase-interaction domain of DnaG reveals that it is made up of two independent subdomains: an N-terminal six-helix module and a C-terminal two-helix module that contains the residues of the primase previously identified as important in the interaction with the helicase. We show that the two-helix module alone is sufficient for strong binding between the primase and the helicase but fails to activate the helicase; both subdomains are required for helicase activation. The six-helix module of the primase has only one close structural homolog, the N-terminal domain of the corresponding helicase. This surprising structural relationship, coupled with the differences in surface properties of the two molecules, suggests how the helicase-interaction domain may perturb the structure of the helicase and lead to activation.
Syson
Karl
K
Department of Molecular Biology and Biotechnology, Krebs Institute, Western Bank, University of Sheffield, Sheffield S10 2TN, United Kingdom.
Thirlway
Jenny
J
Hounslow
Andrea M
AM
Soultanas
Panos
P
Waltho
Jonathan P
JP
D000595:Amino Acid Sequence; D001483:Base Sequence; D004265:DNA Helicases / Q000378:metabolism*; D019915:DNA Primase / Q000737:chemistry / Q000378:metabolism*; D017931:DNA Primers; D004789:Enzyme Activation; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D012996:Solutions
D017931:DNA Primers; D012996:Solutions; D019915:DNA Primase; D004265:DNA Helicases