TY - JOUR
T1 - Structure of the EndoMS-DNA Complex as Mismatch Restriction Endonuclease
AU - Nakae, Setsu
AU - Hijikata, Atsushi
AU - Tsuji, Toshiyuki
AU - Yonezawa, Kouki
AU - Kouyama, Ken ichi
AU - Mayanagi, Kouta
AU - Ishino, Sonoko
AU - Ishino, Yoshizumi
AU - Shirai, Tsuyoshi
N1 - Funding Information:
We thank S. Oda and T. Yamagami for preparing the TkoEndoMS proteins, and the Cooperative Research Project Program of the Medical Institute of Bioregulation, Kyushu University for EM analysis. This work was partly supported by the Platform for Drug Design, Informatics, and Structural Lifescience (PDIS) ( 16am0101042j0005 ) from the AMED , and Grants-in-Aid for Scientific Research (B) ( 25280109 ) (to T.S.) and ( 26242075 ) (to Y.I.) from the MEXT . S.I. was partly supported by the Institute for Fermentation, Osaka (IFO), Japan.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Archaeal NucS nuclease was thought to degrade the single-stranded region of branched DNA, which contains flapped and splayed DNA. However, recent findings indicated that EndoMS, the orthologous enzyme of NucS, specifically cleaves double-stranded DNA (dsDNA) containing mismatched bases. In this study, we determined the structure of the EndoMS-DNA complex. The complex structure of the EndoMS dimer with dsDNA unexpectedly revealed that the mismatched bases were flipped out into binding sites, and the overall architecture most resembled that of restriction enzymes. The structure of the apo form was similar to the reported structure of Pyrococcus abyssi NucS, indicating that movement of the C-terminal domain from the resting state was required for activity. In addition, a model of the EndoMS-PCNA-DNA complex was preliminarily verified with electron microscopy. The structures strongly support the idea that EndoMS acts in a mismatch repair pathway.
AB - Archaeal NucS nuclease was thought to degrade the single-stranded region of branched DNA, which contains flapped and splayed DNA. However, recent findings indicated that EndoMS, the orthologous enzyme of NucS, specifically cleaves double-stranded DNA (dsDNA) containing mismatched bases. In this study, we determined the structure of the EndoMS-DNA complex. The complex structure of the EndoMS dimer with dsDNA unexpectedly revealed that the mismatched bases were flipped out into binding sites, and the overall architecture most resembled that of restriction enzymes. The structure of the apo form was similar to the reported structure of Pyrococcus abyssi NucS, indicating that movement of the C-terminal domain from the resting state was required for activity. In addition, a model of the EndoMS-PCNA-DNA complex was preliminarily verified with electron microscopy. The structures strongly support the idea that EndoMS acts in a mismatch repair pathway.
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U2 - 10.1016/j.str.2016.09.005
DO - 10.1016/j.str.2016.09.005
M3 - Article
C2 - 27773688
AN - SCOPUS:84994056881
SN - 0969-2126
VL - 24
SP - 1960
EP - 1971
JO - Structure with Folding & design
JF - Structure with Folding & design
IS - 11
ER -