Structural basis for ATP-dependent chromatin remodelling by the INO80 complex
In the eukaryotic nucleus, DNA is packaged in the form of nucleosomes, each of which comprises about 147 base pairs of DNA wrapped around a histone protein octamer. The position and histone composition of nucleosomes is governed by ATP-dependent chromatin remodellers 1 – 3 such as the 15-subunit INO...
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| Veröffentlicht in: | Nature (London) 2018-04, Vol.556 (7701), p.386-390 |
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| creator | Eustermann, Sebastian Schall, Kevin Kostrewa, Dirk Lakomek, Kristina Strauss, Mike Moldt, Manuela Hopfner, Karl-Peter |
| description | In the eukaryotic nucleus, DNA is packaged in the form of nucleosomes, each of which comprises about 147 base pairs of DNA wrapped around a histone protein octamer. The position and histone composition of nucleosomes is governed by ATP-dependent chromatin remodellers
1
–
3
such as the 15-subunit INO80 complex
4
. INO80 regulates gene expression, DNA repair and replication by sliding nucleosomes, the exchange of histone H2A.Z with H2A, and the positioning of + 1 and −1 nucleosomes at promoter DNA
5
–
8
. The structures and mechanisms of these remodelling reactions are currently unknown. Here we report the cryo-electron microscopy structure of the evolutionarily conserved core of the INO80 complex from the fungus
Chaetomium thermophilum
bound to a nucleosome, at a global resolution of 4.3 Å and with major parts at 3.7 Å. The INO80 core cradles one entire gyre of the nucleosome through multivalent DNA and histone contacts. An Rvb1/Rvb2 AAA
+
ATPase heterohexamer is an assembly scaffold for the complex and acts as a ‘stator’ for the motor and nucleosome-gripping subunits. The Swi2/Snf2 ATPase motor binds to nucleosomal DNA at superhelical location −6, unwraps approximately 15 base pairs, disrupts the H2A–DNA contacts and is poised to pump entry DNA into the nucleosome. Arp5 and Ies6 bind superhelical locations −2 and −3 to act as a counter grip for the motor, on the other side of the H2A–H2B dimer. The Arp5 insertion domain forms a grappler element that binds the nucleosome dyad, connects the Arp5 actin-fold and entry DNA over a distance of about 90 Å and packs against histone H2A–H2B near the ‘acidic patch’. Our structure together with biochemical data
8
suggests a unified mechanism for nucleosome sliding and histone editing by INO80. The motor is part of a macromolecular ratchet, persistently pumping entry DNA across the H2A–H2B dimer against the Arp5 grip until a large nucleosome translocation step occurs. The transient exposure of H2A–H2B by motor activity as well as differential recognition of H2A.Z and H2A may regulate histone exchange.
Cryo-electron microscopy structures of the evolutionarily conserved core of a fungal INO80 complex bound to the nucleosomal substrate reveal the mechanism underlying nucleosome sliding and histone editing used by this ATP-dependent chromatin remodeller. |
| doi_str_mv | 10.1038/s41586-018-0029-y |
| format | Article |
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1
–
3
such as the 15-subunit INO80 complex
4
. INO80 regulates gene expression, DNA repair and replication by sliding nucleosomes, the exchange of histone H2A.Z with H2A, and the positioning of + 1 and −1 nucleosomes at promoter DNA
5
–
8
. The structures and mechanisms of these remodelling reactions are currently unknown. Here we report the cryo-electron microscopy structure of the evolutionarily conserved core of the INO80 complex from the fungus
Chaetomium thermophilum
bound to a nucleosome, at a global resolution of 4.3 Å and with major parts at 3.7 Å. The INO80 core cradles one entire gyre of the nucleosome through multivalent DNA and histone contacts. An Rvb1/Rvb2 AAA
+
ATPase heterohexamer is an assembly scaffold for the complex and acts as a ‘stator’ for the motor and nucleosome-gripping subunits. The Swi2/Snf2 ATPase motor binds to nucleosomal DNA at superhelical location −6, unwraps approximately 15 base pairs, disrupts the H2A–DNA contacts and is poised to pump entry DNA into the nucleosome. Arp5 and Ies6 bind superhelical locations −2 and −3 to act as a counter grip for the motor, on the other side of the H2A–H2B dimer. The Arp5 insertion domain forms a grappler element that binds the nucleosome dyad, connects the Arp5 actin-fold and entry DNA over a distance of about 90 Å and packs against histone H2A–H2B near the ‘acidic patch’. Our structure together with biochemical data
8
suggests a unified mechanism for nucleosome sliding and histone editing by INO80. The motor is part of a macromolecular ratchet, persistently pumping entry DNA across the H2A–H2B dimer against the Arp5 grip until a large nucleosome translocation step occurs. The transient exposure of H2A–H2B by motor activity as well as differential recognition of H2A.Z and H2A may regulate histone exchange.
Cryo-electron microscopy structures of the evolutionarily conserved core of a fungal INO80 complex bound to the nucleosomal substrate reveal the mechanism underlying nucleosome sliding and histone editing used by this ATP-dependent chromatin remodeller.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/s41586-018-0029-y</identifier><identifier>PMID: 29643509</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>101/28 ; 631/337/100/102 ; 631/535/1258/1259 ; 82/16 ; 82/29 ; Actin ; Adenosine triphosphatase ; Adenosine Triphosphate - metabolism ; Amino Acid Sequence ; Analysis ; ATPases ; Base pairs ; Biochemistry ; Chaetomium - enzymology ; Chaetomium thermophilum ; Chromatin ; Chromatin Assembly and Disassembly ; Chromatin remodeling ; Chromosomal Proteins, Non-Histone - chemistry ; Chromosomal Proteins, Non-Histone - metabolism ; Cryoelectron Microscopy ; Deoxyribonucleic acid ; DNA ; DNA - chemistry ; DNA - metabolism ; DNA - ultrastructure ; DNA biosynthesis ; DNA Helicases - chemistry ; DNA Helicases - metabolism ; DNA Helicases - ultrastructure ; DNA repair ; Editing ; Electron microscopy ; Fungal Proteins ; Fungi ; Gene expression ; Genes ; Histone H2A ; Histones - chemistry ; Histones - metabolism ; Histones - ultrastructure ; Humanities and Social Sciences ; Humans ; Letter ; Macromolecules ; Microscopy ; Models, Molecular ; Motor activity ; multidisciplinary ; Multiprotein Complexes - chemistry ; Multiprotein Complexes - metabolism ; Multiprotein Complexes - ultrastructure ; Muscle proteins ; Nuclei ; Nucleosomes ; Nucleosomes - chemistry ; Nucleosomes - metabolism ; Nucleosomes - ultrastructure ; Protein Binding ; Proteins ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae Proteins - chemistry ; Saccharomyces cerevisiae Proteins - metabolism ; Science ; Science (multidisciplinary) ; Structure-Activity Relationship ; Superhelical DNA ; Translocation</subject><ispartof>Nature (London), 2018-04, Vol.556 (7701), p.386-390</ispartof><rights>Macmillan Publishers Ltd., part of Springer Nature 2018</rights><rights>COPYRIGHT 2018 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 19, 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c581t-ec901b34561f95f033a3022b81c63074b5cc48713c4e3ca186a5c01776e356b73</citedby><cites>FETCH-LOGICAL-c581t-ec901b34561f95f033a3022b81c63074b5cc48713c4e3ca186a5c01776e356b73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41586-018-0029-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41586-018-0029-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,778,782,27911,27912,41475,42544,51306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29643509$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eustermann, Sebastian</creatorcontrib><creatorcontrib>Schall, Kevin</creatorcontrib><creatorcontrib>Kostrewa, Dirk</creatorcontrib><creatorcontrib>Lakomek, Kristina</creatorcontrib><creatorcontrib>Strauss, Mike</creatorcontrib><creatorcontrib>Moldt, Manuela</creatorcontrib><creatorcontrib>Hopfner, Karl-Peter</creatorcontrib><title>Structural basis for ATP-dependent chromatin remodelling by the INO80 complex</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>In the eukaryotic nucleus, DNA is packaged in the form of nucleosomes, each of which comprises about 147 base pairs of DNA wrapped around a histone protein octamer. The position and histone composition of nucleosomes is governed by ATP-dependent chromatin remodellers
1
–
3
such as the 15-subunit INO80 complex
4
. INO80 regulates gene expression, DNA repair and replication by sliding nucleosomes, the exchange of histone H2A.Z with H2A, and the positioning of + 1 and −1 nucleosomes at promoter DNA
5
–
8
. The structures and mechanisms of these remodelling reactions are currently unknown. Here we report the cryo-electron microscopy structure of the evolutionarily conserved core of the INO80 complex from the fungus
Chaetomium thermophilum
bound to a nucleosome, at a global resolution of 4.3 Å and with major parts at 3.7 Å. The INO80 core cradles one entire gyre of the nucleosome through multivalent DNA and histone contacts. An Rvb1/Rvb2 AAA
+
ATPase heterohexamer is an assembly scaffold for the complex and acts as a ‘stator’ for the motor and nucleosome-gripping subunits. The Swi2/Snf2 ATPase motor binds to nucleosomal DNA at superhelical location −6, unwraps approximately 15 base pairs, disrupts the H2A–DNA contacts and is poised to pump entry DNA into the nucleosome. Arp5 and Ies6 bind superhelical locations −2 and −3 to act as a counter grip for the motor, on the other side of the H2A–H2B dimer. The Arp5 insertion domain forms a grappler element that binds the nucleosome dyad, connects the Arp5 actin-fold and entry DNA over a distance of about 90 Å and packs against histone H2A–H2B near the ‘acidic patch’. Our structure together with biochemical data
8
suggests a unified mechanism for nucleosome sliding and histone editing by INO80. The motor is part of a macromolecular ratchet, persistently pumping entry DNA across the H2A–H2B dimer against the Arp5 grip until a large nucleosome translocation step occurs. The transient exposure of H2A–H2B by motor activity as well as differential recognition of H2A.Z and H2A may regulate histone exchange.
Cryo-electron microscopy structures of the evolutionarily conserved core of a fungal INO80 complex bound to the nucleosomal substrate reveal the mechanism underlying nucleosome sliding and histone editing used by this ATP-dependent chromatin remodeller.</description><subject>101/28</subject><subject>631/337/100/102</subject><subject>631/535/1258/1259</subject><subject>82/16</subject><subject>82/29</subject><subject>Actin</subject><subject>Adenosine triphosphatase</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>Amino Acid Sequence</subject><subject>Analysis</subject><subject>ATPases</subject><subject>Base pairs</subject><subject>Biochemistry</subject><subject>Chaetomium - enzymology</subject><subject>Chaetomium thermophilum</subject><subject>Chromatin</subject><subject>Chromatin Assembly and Disassembly</subject><subject>Chromatin remodeling</subject><subject>Chromosomal Proteins, Non-Histone - chemistry</subject><subject>Chromosomal Proteins, Non-Histone - metabolism</subject><subject>Cryoelectron Microscopy</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - chemistry</subject><subject>DNA - metabolism</subject><subject>DNA - ultrastructure</subject><subject>DNA biosynthesis</subject><subject>DNA Helicases - chemistry</subject><subject>DNA Helicases - metabolism</subject><subject>DNA Helicases - ultrastructure</subject><subject>DNA repair</subject><subject>Editing</subject><subject>Electron microscopy</subject><subject>Fungal Proteins</subject><subject>Fungi</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Histone H2A</subject><subject>Histones - chemistry</subject><subject>Histones - metabolism</subject><subject>Histones - ultrastructure</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Letter</subject><subject>Macromolecules</subject><subject>Microscopy</subject><subject>Models, Molecular</subject><subject>Motor activity</subject><subject>multidisciplinary</subject><subject>Multiprotein Complexes - chemistry</subject><subject>Multiprotein Complexes - metabolism</subject><subject>Multiprotein Complexes - ultrastructure</subject><subject>Muscle proteins</subject><subject>Nuclei</subject><subject>Nucleosomes</subject><subject>Nucleosomes - chemistry</subject><subject>Nucleosomes - metabolism</subject><subject>Nucleosomes - ultrastructure</subject><subject>Protein Binding</subject><subject>Proteins</subject><subject>Saccharomyces cerevisiae</subject><subject>Saccharomyces cerevisiae Proteins - chemistry</subject><subject>Saccharomyces cerevisiae Proteins - metabolism</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Structure-Activity Relationship</subject><subject>Superhelical 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Research Library</collection><collection>Science Database (ProQuest)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>Materials Science Collection</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>University of Michigan</collection><collection>Genetics Abstracts</collection><collection>SIRS Editorial</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eustermann, Sebastian</au><au>Schall, Kevin</au><au>Kostrewa, Dirk</au><au>Lakomek, Kristina</au><au>Strauss, Mike</au><au>Moldt, Manuela</au><au>Hopfner, Karl-Peter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural basis for ATP-dependent chromatin remodelling by the INO80 complex</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>2018-04</date><risdate>2018</risdate><volume>556</volume><issue>7701</issue><spage>386</spage><epage>390</epage><pages>386-390</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><abstract>In the eukaryotic nucleus, DNA is packaged in the form of nucleosomes, each of which comprises about 147 base pairs of DNA wrapped around a histone protein octamer. The position and histone composition of nucleosomes is governed by ATP-dependent chromatin remodellers
1
–
3
such as the 15-subunit INO80 complex
4
. INO80 regulates gene expression, DNA repair and replication by sliding nucleosomes, the exchange of histone H2A.Z with H2A, and the positioning of + 1 and −1 nucleosomes at promoter DNA
5
–
8
. The structures and mechanisms of these remodelling reactions are currently unknown. Here we report the cryo-electron microscopy structure of the evolutionarily conserved core of the INO80 complex from the fungus
Chaetomium thermophilum
bound to a nucleosome, at a global resolution of 4.3 Å and with major parts at 3.7 Å. The INO80 core cradles one entire gyre of the nucleosome through multivalent DNA and histone contacts. An Rvb1/Rvb2 AAA
+
ATPase heterohexamer is an assembly scaffold for the complex and acts as a ‘stator’ for the motor and nucleosome-gripping subunits. The Swi2/Snf2 ATPase motor binds to nucleosomal DNA at superhelical location −6, unwraps approximately 15 base pairs, disrupts the H2A–DNA contacts and is poised to pump entry DNA into the nucleosome. Arp5 and Ies6 bind superhelical locations −2 and −3 to act as a counter grip for the motor, on the other side of the H2A–H2B dimer. The Arp5 insertion domain forms a grappler element that binds the nucleosome dyad, connects the Arp5 actin-fold and entry DNA over a distance of about 90 Å and packs against histone H2A–H2B near the ‘acidic patch’. Our structure together with biochemical data
8
suggests a unified mechanism for nucleosome sliding and histone editing by INO80. The motor is part of a macromolecular ratchet, persistently pumping entry DNA across the H2A–H2B dimer against the Arp5 grip until a large nucleosome translocation step occurs. The transient exposure of H2A–H2B by motor activity as well as differential recognition of H2A.Z and H2A may regulate histone exchange.
Cryo-electron microscopy structures of the evolutionarily conserved core of a fungal INO80 complex bound to the nucleosomal substrate reveal the mechanism underlying nucleosome sliding and histone editing used by this ATP-dependent chromatin remodeller.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29643509</pmid><doi>10.1038/s41586-018-0029-y</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature (London), 2018-04, Vol.556 (7701), p.386-390 |
| issn | 0028-0836 1476-4687 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2024472482 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | 101/28 631/337/100/102 631/535/1258/1259 82/16 82/29 Actin Adenosine triphosphatase Adenosine Triphosphate - metabolism Amino Acid Sequence Analysis ATPases Base pairs Biochemistry Chaetomium - enzymology Chaetomium thermophilum Chromatin Chromatin Assembly and Disassembly Chromatin remodeling Chromosomal Proteins, Non-Histone - chemistry Chromosomal Proteins, Non-Histone - metabolism Cryoelectron Microscopy Deoxyribonucleic acid DNA DNA - chemistry DNA - metabolism DNA - ultrastructure DNA biosynthesis DNA Helicases - chemistry DNA Helicases - metabolism DNA Helicases - ultrastructure DNA repair Editing Electron microscopy Fungal Proteins Fungi Gene expression Genes Histone H2A Histones - chemistry Histones - metabolism Histones - ultrastructure Humanities and Social Sciences Humans Letter Macromolecules Microscopy Models, Molecular Motor activity multidisciplinary Multiprotein Complexes - chemistry Multiprotein Complexes - metabolism Multiprotein Complexes - ultrastructure Muscle proteins Nuclei Nucleosomes Nucleosomes - chemistry Nucleosomes - metabolism Nucleosomes - ultrastructure Protein Binding Proteins Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins - chemistry Saccharomyces cerevisiae Proteins - metabolism Science Science (multidisciplinary) Structure-Activity Relationship Superhelical DNA Translocation |
| title | Structural basis for ATP-dependent chromatin remodelling by the INO80 complex |
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