Sharp kinking of a coiled-coil in MutS allows DNA binding and release
DNA mismatch repair (MMR) corrects mismatches, small insertions and deletions in DNA during DNA replication. While scanning for mismatches, dimers of MutS embrace the DNA helix with their lever and clamp domains. Previous studies indicated generic flexibility of the lever and clamp domains of MutS p...
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| Veröffentlicht in: | Nucleic acids research 2019-09, Vol.47 (16), p.8888-8898 |
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| container_title | Nucleic acids research |
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| creator | Bhairosing-Kok, Doreth Groothuizen, Flora S Fish, Alexander Dharadhar, Shreya Winterwerp, Herrie H K Sixma, Titia K |
| description | DNA mismatch repair (MMR) corrects mismatches, small insertions and deletions in DNA during DNA replication. While scanning for mismatches, dimers of MutS embrace the DNA helix with their lever and clamp domains. Previous studies indicated generic flexibility of the lever and clamp domains of MutS prior to DNA binding, but whether this was important for MutS function was unknown. Here, we present a novel crystal structure of DNA-free Escherichia coli MutS. In this apo-structure, the clamp domains are repositioned due to kinking at specific sites in the coiled-coil region in the lever domains, suggesting a defined hinge point. We made mutations at the coiled-coil hinge point. The mutants made to disrupt the helical fold at the kink site diminish DNA binding, whereas those made to increase stability of coiled-coil result in stronger DNA binding. These data suggest that the site-specific kinking of the coiled-coil in the lever domain is important for loading of this ABC-ATPase on DNA. |
| doi_str_mv | 10.1093/nar/gkz649 |
| format | Article |
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While scanning for mismatches, dimers of MutS embrace the DNA helix with their lever and clamp domains. Previous studies indicated generic flexibility of the lever and clamp domains of MutS prior to DNA binding, but whether this was important for MutS function was unknown. Here, we present a novel crystal structure of DNA-free Escherichia coli MutS. In this apo-structure, the clamp domains are repositioned due to kinking at specific sites in the coiled-coil region in the lever domains, suggesting a defined hinge point. We made mutations at the coiled-coil hinge point. The mutants made to disrupt the helical fold at the kink site diminish DNA binding, whereas those made to increase stability of coiled-coil result in stronger DNA binding. 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Published by Oxford University Press on behalf of Nucleic Acids Research.</rights><rights>The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-45a5d717ad8052237b09ada05d96f2e82ecca70ccdb834e2f3bf2819781dfced3</citedby><cites>FETCH-LOGICAL-c378t-45a5d717ad8052237b09ada05d96f2e82ecca70ccdb834e2f3bf2819781dfced3</cites><orcidid>0000-0001-6180-0632</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895276/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895276/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31372631$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bhairosing-Kok, Doreth</creatorcontrib><creatorcontrib>Groothuizen, Flora S</creatorcontrib><creatorcontrib>Fish, Alexander</creatorcontrib><creatorcontrib>Dharadhar, Shreya</creatorcontrib><creatorcontrib>Winterwerp, Herrie H K</creatorcontrib><creatorcontrib>Sixma, Titia K</creatorcontrib><title>Sharp kinking of a coiled-coil in MutS allows DNA binding and release</title><title>Nucleic acids research</title><addtitle>Nucleic Acids Res</addtitle><description>DNA mismatch repair (MMR) corrects mismatches, small insertions and deletions in DNA during DNA replication. While scanning for mismatches, dimers of MutS embrace the DNA helix with their lever and clamp domains. Previous studies indicated generic flexibility of the lever and clamp domains of MutS prior to DNA binding, but whether this was important for MutS function was unknown. Here, we present a novel crystal structure of DNA-free Escherichia coli MutS. In this apo-structure, the clamp domains are repositioned due to kinking at specific sites in the coiled-coil region in the lever domains, suggesting a defined hinge point. We made mutations at the coiled-coil hinge point. The mutants made to disrupt the helical fold at the kink site diminish DNA binding, whereas those made to increase stability of coiled-coil result in stronger DNA binding. These data suggest that the site-specific kinking of the coiled-coil in the lever domain is important for loading of this ABC-ATPase on DNA.</description><subject>Amino Acid Sequence</subject><subject>Apoproteins - chemistry</subject><subject>Apoproteins - genetics</subject><subject>Apoproteins - metabolism</subject><subject>Binding Sites</subject><subject>Cloning, Molecular</subject><subject>Crystallography, X-Ray</subject><subject>DNA, Bacterial - chemistry</subject><subject>DNA, Bacterial - genetics</subject><subject>DNA, Bacterial - metabolism</subject><subject>Escherichia coli - genetics</subject><subject>Escherichia coli - metabolism</subject><subject>Escherichia coli Proteins - chemistry</subject><subject>Escherichia coli Proteins - genetics</subject><subject>Escherichia coli Proteins - metabolism</subject><subject>Gene Expression</subject><subject>Genetic Vectors - chemistry</subject><subject>Genetic Vectors - metabolism</subject><subject>Kinetics</subject><subject>Models, Molecular</subject><subject>Mutagenesis, Site-Directed</subject><subject>Mutation</subject><subject>MutS DNA Mismatch-Binding Protein - chemistry</subject><subject>MutS DNA Mismatch-Binding Protein - genetics</subject><subject>MutS DNA Mismatch-Binding Protein - metabolism</subject><subject>Protein Binding</subject><subject>Protein Conformation, alpha-Helical</subject><subject>Protein Conformation, beta-Strand</subject><subject>Protein Interaction Domains and Motifs</subject><subject>Protein Multimerization</subject><subject>Recombinant Proteins - chemistry</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - metabolism</subject><subject>Sequence Alignment</subject><subject>Structural Biology</subject><subject>Structure-Activity Relationship</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkF1LwzAUhoMobn7c-AMklyLU5aNN0hthzPkBUy-m1-E0Sbe6rp1Jq-ivd2VzKBx4L87Dew4PQmeUXFGS8kEFfjBbfIs43UN9ygWL4lSwfdQnnCQRJbHqoaMQ3gihMU3iQ9TjlEsmOO2j8XQOfoUXRbWeGa5zDNjURels1AUuKvzYNlMMZVl_BnzzNMRZUdmOhcpi70oHwZ2ggxzK4E63eYxeb8cvo_to8nz3MBpOIsOlaqI4gcRKKsEqkjDGZUZSsEASm4qcOcWcMSCJMTZTPHYs51nOFE2lojY3zvJjdL3pXbXZ0lnjqsZDqVe-WIL_0jUU-v-mKuZ6Vn9oodKESbEuuNgW-Pq9daHRyyIYV5ZQuboNmjGhOEkZ7dDLDWp8HYJ3-e4MJbrzrtfe9cb7Gj7_-9gO_RXNfwBI7n_L</recordid><startdate>20190919</startdate><enddate>20190919</enddate><creator>Bhairosing-Kok, Doreth</creator><creator>Groothuizen, Flora S</creator><creator>Fish, Alexander</creator><creator>Dharadhar, Shreya</creator><creator>Winterwerp, Herrie H K</creator><creator>Sixma, Titia K</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6180-0632</orcidid></search><sort><creationdate>20190919</creationdate><title>Sharp kinking of a coiled-coil in MutS allows DNA binding and release</title><author>Bhairosing-Kok, Doreth ; Groothuizen, Flora S ; Fish, Alexander ; Dharadhar, Shreya ; Winterwerp, Herrie H K ; Sixma, Titia K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-45a5d717ad8052237b09ada05d96f2e82ecca70ccdb834e2f3bf2819781dfced3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Amino Acid Sequence</topic><topic>Apoproteins - chemistry</topic><topic>Apoproteins - genetics</topic><topic>Apoproteins - metabolism</topic><topic>Binding Sites</topic><topic>Cloning, Molecular</topic><topic>Crystallography, X-Ray</topic><topic>DNA, Bacterial - chemistry</topic><topic>DNA, Bacterial - genetics</topic><topic>DNA, Bacterial - metabolism</topic><topic>Escherichia coli - genetics</topic><topic>Escherichia coli - metabolism</topic><topic>Escherichia coli Proteins - chemistry</topic><topic>Escherichia coli Proteins - genetics</topic><topic>Escherichia coli Proteins - metabolism</topic><topic>Gene Expression</topic><topic>Genetic Vectors - chemistry</topic><topic>Genetic Vectors - metabolism</topic><topic>Kinetics</topic><topic>Models, Molecular</topic><topic>Mutagenesis, Site-Directed</topic><topic>Mutation</topic><topic>MutS DNA Mismatch-Binding Protein - chemistry</topic><topic>MutS DNA Mismatch-Binding Protein - genetics</topic><topic>MutS DNA Mismatch-Binding Protein - metabolism</topic><topic>Protein Binding</topic><topic>Protein Conformation, alpha-Helical</topic><topic>Protein Conformation, beta-Strand</topic><topic>Protein Interaction Domains and Motifs</topic><topic>Protein Multimerization</topic><topic>Recombinant Proteins - chemistry</topic><topic>Recombinant Proteins - genetics</topic><topic>Recombinant Proteins - metabolism</topic><topic>Sequence Alignment</topic><topic>Structural Biology</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bhairosing-Kok, Doreth</creatorcontrib><creatorcontrib>Groothuizen, Flora S</creatorcontrib><creatorcontrib>Fish, Alexander</creatorcontrib><creatorcontrib>Dharadhar, Shreya</creatorcontrib><creatorcontrib>Winterwerp, Herrie H K</creatorcontrib><creatorcontrib>Sixma, Titia K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bhairosing-Kok, Doreth</au><au>Groothuizen, Flora S</au><au>Fish, Alexander</au><au>Dharadhar, Shreya</au><au>Winterwerp, Herrie H K</au><au>Sixma, Titia K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sharp kinking of a coiled-coil in MutS allows DNA binding and release</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2019-09-19</date><risdate>2019</risdate><volume>47</volume><issue>16</issue><spage>8888</spage><epage>8898</epage><pages>8888-8898</pages><issn>0305-1048</issn><eissn>1362-4962</eissn><abstract>DNA mismatch repair (MMR) corrects mismatches, small insertions and deletions in DNA during DNA replication. While scanning for mismatches, dimers of MutS embrace the DNA helix with their lever and clamp domains. Previous studies indicated generic flexibility of the lever and clamp domains of MutS prior to DNA binding, but whether this was important for MutS function was unknown. Here, we present a novel crystal structure of DNA-free Escherichia coli MutS. In this apo-structure, the clamp domains are repositioned due to kinking at specific sites in the coiled-coil region in the lever domains, suggesting a defined hinge point. We made mutations at the coiled-coil hinge point. The mutants made to disrupt the helical fold at the kink site diminish DNA binding, whereas those made to increase stability of coiled-coil result in stronger DNA binding. These data suggest that the site-specific kinking of the coiled-coil in the lever domain is important for loading of this ABC-ATPase on DNA.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>31372631</pmid><doi>10.1093/nar/gkz649</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-6180-0632</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central; Free Full-Text Journals in Chemistry; Oxford Open Access Journals |
| subjects | Amino Acid Sequence Apoproteins - chemistry Apoproteins - genetics Apoproteins - metabolism Binding Sites Cloning, Molecular Crystallography, X-Ray DNA, Bacterial - chemistry DNA, Bacterial - genetics DNA, Bacterial - metabolism Escherichia coli - genetics Escherichia coli - metabolism Escherichia coli Proteins - chemistry Escherichia coli Proteins - genetics Escherichia coli Proteins - metabolism Gene Expression Genetic Vectors - chemistry Genetic Vectors - metabolism Kinetics Models, Molecular Mutagenesis, Site-Directed Mutation MutS DNA Mismatch-Binding Protein - chemistry MutS DNA Mismatch-Binding Protein - genetics MutS DNA Mismatch-Binding Protein - metabolism Protein Binding Protein Conformation, alpha-Helical Protein Conformation, beta-Strand Protein Interaction Domains and Motifs Protein Multimerization Recombinant Proteins - chemistry Recombinant Proteins - genetics Recombinant Proteins - metabolism Sequence Alignment Structural Biology Structure-Activity Relationship |
| title | Sharp kinking of a coiled-coil in MutS allows DNA binding and release |
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