TY - JOUR
T1 - A conserved MutS homolog connector domain interface interacts with MutL homologs
AU - Mendillo, Marc L.
AU - Hargreaves, Victoria V.
AU - Jamison, Jonathan W.
AU - Mo, Ashley O.
AU - Li, Sheng
AU - Putnam, Christopher D.
AU - Woods, Virgil L.
AU - Kolodner, Richard D.
PY - 2009/12/19
Y1 - 2009/12/19
N2 - Escherichia coli MutS forms a mispair-dependent ternary complex with MutL that is essential for initiating mismatch repair (MMR) but is structurally uncharacterized, in part owing to its dynamic nature. Here, we used hydrogen/deuterium exchange mass spectrometry and other methods to identify a region in the connector domain (domain II) of MutS that binds MutL and is required for mispair-dependent ternary complex formation and MMR. A structurally conserved region in Msh2, the eukaryotic homolog, was required for formation of a mispair-dependent Msh2-Msh6-Mlh1-Pms1 ternary complex. These data indicate that the connector domain of MutS and Msh2 contains the interface for binding MutL and Mlh1-Pms1, respectively, and support a mechanism whereby mispair and ATP binding induces a conformational change that allows the MutS and Msh2 interfaces to interact with their partners.
AB - Escherichia coli MutS forms a mispair-dependent ternary complex with MutL that is essential for initiating mismatch repair (MMR) but is structurally uncharacterized, in part owing to its dynamic nature. Here, we used hydrogen/deuterium exchange mass spectrometry and other methods to identify a region in the connector domain (domain II) of MutS that binds MutL and is required for mispair-dependent ternary complex formation and MMR. A structurally conserved region in Msh2, the eukaryotic homolog, was required for formation of a mispair-dependent Msh2-Msh6-Mlh1-Pms1 ternary complex. These data indicate that the connector domain of MutS and Msh2 contains the interface for binding MutL and Mlh1-Pms1, respectively, and support a mechanism whereby mispair and ATP binding induces a conformational change that allows the MutS and Msh2 interfaces to interact with their partners.
KW - Deuterium exchange
KW - Mass spectrometry
KW - Mismatch repair
KW - Mlh1-Pms1
KW - Msh2-Msh6
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U2 - 10.1073/pnas.0912250106
DO - 10.1073/pnas.0912250106
M3 - Article
C2 - 20080788
AN - SCOPUS:76049121502
SN - 0027-8424
VL - 106
SP - 22223
EP - 22228
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 52
ER -