An ensemble of cryo-EM structures of TRiC reveal its conformational landscape and subunit specificity
TRiC/CCT assists the folding of ∼10% of cytosolic proteins through an ATP-driven conformational cycle and is essential in maintaining protein homeostasis. Here, we determined an ensemble of cryo-electron microscopy (cryo-EM) structures of yeast TRiC at various nucleotide concentrations, with 4 open-...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2019-09, Vol.116 (39), p.19513-19522 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 19522 |
|---|---|
| container_issue | 39 |
| container_start_page | 19513 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 116 |
| creator | Jin, Mingliang Han, Wenyu Liu, Caixuan Zang, Yunxiang Li, Jiawei Wang, Fangfang Wang, Yanxing Cong, Yao |
| description | TRiC/CCT assists the folding of ∼10% of cytosolic proteins through an ATP-driven conformational cycle and is essential in maintaining protein homeostasis. Here, we determined an ensemble of cryo-electron microscopy (cryo-EM) structures of yeast TRiC at various nucleotide concentrations, with 4 open-state maps resolved at near-atomic resolutions, and a closed-state map at atomic resolution, revealing an extra layer of an unforeseen N-terminal allosteric network. We found that, during TRiC ring closure, the CCT7 subunit moves first, responding to nucleotide binding; CCT4 is the last to bind ATP, serving as an ATP sensor; and CCT8 remains ADP-bound and is hardly involved in the ATPase-cycle in our experimental conditions; overall, yeast TRiC consumes nucleotide in a 2-ring positively coordinated manner. Our results depict a thorough picture of the TRiC conformational landscape and its allosteric transitions from the open to closed states in more structural detail and offer insights into TRiC subunit specificity in ATP consumption and ring closure, and potentially in substrate processing. |
| doi_str_mv | 10.1073/pnas.1903976116 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6765261</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>26855193</jstor_id><sourcerecordid>26855193</sourcerecordid><originalsourceid>FETCH-LOGICAL-c509t-35d86b2becfe121d6219cf380169439f63de0389f676569d6bd772a3aa3e760c3</originalsourceid><addsrcrecordid>eNpdkU1r3DAQhkVpaTZpzz21CHrJxYk-bFm6FMKSpIWEQEnPQpbHrRZbciU5sP--MptuPy6jYeaZlxm9CL2j5IKSll_O3qQLqghXraBUvEAbShStRK3IS7QhhLWVrFl9gk5T2hFCVCPJa3TCaa2YpGKD4Mpj8AmmbgQcBmzjPlTX9zjluNi8REhr9fGr2-IIT2BG7HLCNvghxMlkF3wpjcb3yZoZcElwWrrFu4zTDNYNzrq8f4NeDWZM8Pb5PUPfbq4ft5-ru4fbL9uru8o2ROWKN70UHevADkAZ7QWjyg5cEipUzdUgeA-Ey5K0ohGqF13ftsxwYzi0glh-hj4ddOelm6C34HM0o56jm0zc62Cc_rfj3Q_9PTzpVZAJWgTOnwVi-LlAynpyycJYLoSwJM2YFKoERgr68T90F5ZYvmOllGobqXhdqMsDZWNIKcJwXIYSvVqoVwv1HwvLxIe_bzjyvz0rwPsDsEs5xGOfCdk0VHH-C7jYooo</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2299758934</pqid></control><display><type>article</type><title>An ensemble of cryo-EM structures of TRiC reveal its conformational landscape and subunit specificity</title><source>MEDLINE</source><source>JSTOR Archive Collection A-Z Listing</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Jin, Mingliang ; Han, Wenyu ; Liu, Caixuan ; Zang, Yunxiang ; Li, Jiawei ; Wang, Fangfang ; Wang, Yanxing ; Cong, Yao</creator><creatorcontrib>Jin, Mingliang ; Han, Wenyu ; Liu, Caixuan ; Zang, Yunxiang ; Li, Jiawei ; Wang, Fangfang ; Wang, Yanxing ; Cong, Yao</creatorcontrib><description>TRiC/CCT assists the folding of ∼10% of cytosolic proteins through an ATP-driven conformational cycle and is essential in maintaining protein homeostasis. Here, we determined an ensemble of cryo-electron microscopy (cryo-EM) structures of yeast TRiC at various nucleotide concentrations, with 4 open-state maps resolved at near-atomic resolutions, and a closed-state map at atomic resolution, revealing an extra layer of an unforeseen N-terminal allosteric network. We found that, during TRiC ring closure, the CCT7 subunit moves first, responding to nucleotide binding; CCT4 is the last to bind ATP, serving as an ATP sensor; and CCT8 remains ADP-bound and is hardly involved in the ATPase-cycle in our experimental conditions; overall, yeast TRiC consumes nucleotide in a 2-ring positively coordinated manner. Our results depict a thorough picture of the TRiC conformational landscape and its allosteric transitions from the open to closed states in more structural detail and offer insights into TRiC subunit specificity in ATP consumption and ring closure, and potentially in substrate processing.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1903976116</identifier><identifier>PMID: 31492816</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Adenosine diphosphate ; Adenosine triphosphatase ; Adenosine Triphosphatases - metabolism ; Adenosine triphosphate ; Allosteric properties ; ATP ; Biological Sciences ; Chaperonin Containing TCP-1 - metabolism ; Chaperonin Containing TCP-1 - physiology ; Chaperonin Containing TCP-1 - ultrastructure ; Chaperonins - metabolism ; Cryoelectron Microscopy - methods ; Electron microscopy ; Homeostasis ; Models, Molecular ; Molecular Conformation ; Nucleotides ; PNAS Plus ; Protein Folding ; Protein Subunits - metabolism ; Proteins ; Proteostasis ; Saccharomyces cerevisiae - metabolism ; Saccharomyces cerevisiae Proteins - metabolism ; Structure-Activity Relationship ; Substrate Specificity - physiology ; Substrates ; Yeast ; Yeasts</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2019-09, Vol.116 (39), p.19513-19522</ispartof><rights>Copyright © 2019 the Author(s). Published by PNAS.</rights><rights>Copyright National Academy of Sciences Sep 24, 2019</rights><rights>Copyright © 2019 the Author(s). Published by PNAS. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-35d86b2becfe121d6219cf380169439f63de0389f676569d6bd772a3aa3e760c3</citedby><cites>FETCH-LOGICAL-c509t-35d86b2becfe121d6219cf380169439f63de0389f676569d6bd772a3aa3e760c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26855193$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26855193$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31492816$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jin, Mingliang</creatorcontrib><creatorcontrib>Han, Wenyu</creatorcontrib><creatorcontrib>Liu, Caixuan</creatorcontrib><creatorcontrib>Zang, Yunxiang</creatorcontrib><creatorcontrib>Li, Jiawei</creatorcontrib><creatorcontrib>Wang, Fangfang</creatorcontrib><creatorcontrib>Wang, Yanxing</creatorcontrib><creatorcontrib>Cong, Yao</creatorcontrib><title>An ensemble of cryo-EM structures of TRiC reveal its conformational landscape and subunit specificity</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>TRiC/CCT assists the folding of ∼10% of cytosolic proteins through an ATP-driven conformational cycle and is essential in maintaining protein homeostasis. Here, we determined an ensemble of cryo-electron microscopy (cryo-EM) structures of yeast TRiC at various nucleotide concentrations, with 4 open-state maps resolved at near-atomic resolutions, and a closed-state map at atomic resolution, revealing an extra layer of an unforeseen N-terminal allosteric network. We found that, during TRiC ring closure, the CCT7 subunit moves first, responding to nucleotide binding; CCT4 is the last to bind ATP, serving as an ATP sensor; and CCT8 remains ADP-bound and is hardly involved in the ATPase-cycle in our experimental conditions; overall, yeast TRiC consumes nucleotide in a 2-ring positively coordinated manner. Our results depict a thorough picture of the TRiC conformational landscape and its allosteric transitions from the open to closed states in more structural detail and offer insights into TRiC subunit specificity in ATP consumption and ring closure, and potentially in substrate processing.</description><subject>Adenosine diphosphate</subject><subject>Adenosine triphosphatase</subject><subject>Adenosine Triphosphatases - metabolism</subject><subject>Adenosine triphosphate</subject><subject>Allosteric properties</subject><subject>ATP</subject><subject>Biological Sciences</subject><subject>Chaperonin Containing TCP-1 - metabolism</subject><subject>Chaperonin Containing TCP-1 - physiology</subject><subject>Chaperonin Containing TCP-1 - ultrastructure</subject><subject>Chaperonins - metabolism</subject><subject>Cryoelectron Microscopy - methods</subject><subject>Electron microscopy</subject><subject>Homeostasis</subject><subject>Models, Molecular</subject><subject>Molecular Conformation</subject><subject>Nucleotides</subject><subject>PNAS Plus</subject><subject>Protein Folding</subject><subject>Protein Subunits - metabolism</subject><subject>Proteins</subject><subject>Proteostasis</subject><subject>Saccharomyces cerevisiae - metabolism</subject><subject>Saccharomyces cerevisiae Proteins - metabolism</subject><subject>Structure-Activity Relationship</subject><subject>Substrate Specificity - physiology</subject><subject>Substrates</subject><subject>Yeast</subject><subject>Yeasts</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1r3DAQhkVpaTZpzz21CHrJxYk-bFm6FMKSpIWEQEnPQpbHrRZbciU5sP--MptuPy6jYeaZlxm9CL2j5IKSll_O3qQLqghXraBUvEAbShStRK3IS7QhhLWVrFl9gk5T2hFCVCPJa3TCaa2YpGKD4Mpj8AmmbgQcBmzjPlTX9zjluNi8REhr9fGr2-IIT2BG7HLCNvghxMlkF3wpjcb3yZoZcElwWrrFu4zTDNYNzrq8f4NeDWZM8Pb5PUPfbq4ft5-ru4fbL9uru8o2ROWKN70UHevADkAZ7QWjyg5cEipUzdUgeA-Ey5K0ohGqF13ftsxwYzi0glh-hj4ddOelm6C34HM0o56jm0zc62Cc_rfj3Q_9PTzpVZAJWgTOnwVi-LlAynpyycJYLoSwJM2YFKoERgr68T90F5ZYvmOllGobqXhdqMsDZWNIKcJwXIYSvVqoVwv1HwvLxIe_bzjyvz0rwPsDsEs5xGOfCdk0VHH-C7jYooo</recordid><startdate>20190924</startdate><enddate>20190924</enddate><creator>Jin, Mingliang</creator><creator>Han, Wenyu</creator><creator>Liu, Caixuan</creator><creator>Zang, Yunxiang</creator><creator>Li, Jiawei</creator><creator>Wang, Fangfang</creator><creator>Wang, Yanxing</creator><creator>Cong, Yao</creator><general>National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190924</creationdate><title>An ensemble of cryo-EM structures of TRiC reveal its conformational landscape and subunit specificity</title><author>Jin, Mingliang ; Han, Wenyu ; Liu, Caixuan ; Zang, Yunxiang ; Li, Jiawei ; Wang, Fangfang ; Wang, Yanxing ; Cong, Yao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c509t-35d86b2becfe121d6219cf380169439f63de0389f676569d6bd772a3aa3e760c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adenosine diphosphate</topic><topic>Adenosine triphosphatase</topic><topic>Adenosine Triphosphatases - metabolism</topic><topic>Adenosine triphosphate</topic><topic>Allosteric properties</topic><topic>ATP</topic><topic>Biological Sciences</topic><topic>Chaperonin Containing TCP-1 - metabolism</topic><topic>Chaperonin Containing TCP-1 - physiology</topic><topic>Chaperonin Containing TCP-1 - ultrastructure</topic><topic>Chaperonins - metabolism</topic><topic>Cryoelectron Microscopy - methods</topic><topic>Electron microscopy</topic><topic>Homeostasis</topic><topic>Models, Molecular</topic><topic>Molecular Conformation</topic><topic>Nucleotides</topic><topic>PNAS Plus</topic><topic>Protein Folding</topic><topic>Protein Subunits - metabolism</topic><topic>Proteins</topic><topic>Proteostasis</topic><topic>Saccharomyces cerevisiae - metabolism</topic><topic>Saccharomyces cerevisiae Proteins - metabolism</topic><topic>Structure-Activity Relationship</topic><topic>Substrate Specificity - physiology</topic><topic>Substrates</topic><topic>Yeast</topic><topic>Yeasts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jin, Mingliang</creatorcontrib><creatorcontrib>Han, Wenyu</creatorcontrib><creatorcontrib>Liu, Caixuan</creatorcontrib><creatorcontrib>Zang, Yunxiang</creatorcontrib><creatorcontrib>Li, Jiawei</creatorcontrib><creatorcontrib>Wang, Fangfang</creatorcontrib><creatorcontrib>Wang, Yanxing</creatorcontrib><creatorcontrib>Cong, Yao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jin, Mingliang</au><au>Han, Wenyu</au><au>Liu, Caixuan</au><au>Zang, Yunxiang</au><au>Li, Jiawei</au><au>Wang, Fangfang</au><au>Wang, Yanxing</au><au>Cong, Yao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An ensemble of cryo-EM structures of TRiC reveal its conformational landscape and subunit specificity</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2019-09-24</date><risdate>2019</risdate><volume>116</volume><issue>39</issue><spage>19513</spage><epage>19522</epage><pages>19513-19522</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>TRiC/CCT assists the folding of ∼10% of cytosolic proteins through an ATP-driven conformational cycle and is essential in maintaining protein homeostasis. Here, we determined an ensemble of cryo-electron microscopy (cryo-EM) structures of yeast TRiC at various nucleotide concentrations, with 4 open-state maps resolved at near-atomic resolutions, and a closed-state map at atomic resolution, revealing an extra layer of an unforeseen N-terminal allosteric network. We found that, during TRiC ring closure, the CCT7 subunit moves first, responding to nucleotide binding; CCT4 is the last to bind ATP, serving as an ATP sensor; and CCT8 remains ADP-bound and is hardly involved in the ATPase-cycle in our experimental conditions; overall, yeast TRiC consumes nucleotide in a 2-ring positively coordinated manner. Our results depict a thorough picture of the TRiC conformational landscape and its allosteric transitions from the open to closed states in more structural detail and offer insights into TRiC subunit specificity in ATP consumption and ring closure, and potentially in substrate processing.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>31492816</pmid><doi>10.1073/pnas.1903976116</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2019-09, Vol.116 (39), p.19513-19522 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6765261 |
| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Adenosine diphosphate Adenosine triphosphatase Adenosine Triphosphatases - metabolism Adenosine triphosphate Allosteric properties ATP Biological Sciences Chaperonin Containing TCP-1 - metabolism Chaperonin Containing TCP-1 - physiology Chaperonin Containing TCP-1 - ultrastructure Chaperonins - metabolism Cryoelectron Microscopy - methods Electron microscopy Homeostasis Models, Molecular Molecular Conformation Nucleotides PNAS Plus Protein Folding Protein Subunits - metabolism Proteins Proteostasis Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins - metabolism Structure-Activity Relationship Substrate Specificity - physiology Substrates Yeast Yeasts |
| title | An ensemble of cryo-EM structures of TRiC reveal its conformational landscape and subunit specificity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T20%3A56%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=An%20ensemble%20of%20cryo-EM%20structures%20of%20TRiC%20reveal%20its%20conformational%20landscape%20and%20subunit%20specificity&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Jin,%20Mingliang&rft.date=2019-09-24&rft.volume=116&rft.issue=39&rft.spage=19513&rft.epage=19522&rft.pages=19513-19522&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.1903976116&rft_dat=%3Cjstor_pubme%3E26855193%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2299758934&rft_id=info:pmid/31492816&rft_jstor_id=26855193&rfr_iscdi=true |