Nascent chain dynamics and ribosome interactions within folded ribosome-nascent chain complexes observed by NMR spectroscopy
The folding of many proteins can begin during biosynthesis on the ribosome and can be modulated by the ribosome itself. Such perturbations are generally believed to be mediated through interactions between the nascent chain and the ribosome surface, but despite recent progress in characterising inte...
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description | The folding of many proteins can begin during biosynthesis on the ribosome and can be modulated by the ribosome itself. Such perturbations are generally believed to be mediated through interactions between the nascent chain and the ribosome surface, but despite recent progress in characterising interactions of unfolded states with the ribosome, and their impact on the initiation of co-translational folding, a complete quantitative analysis of interactions across both folded and unfolded states of a nascent chain has yet to be realised. Here we apply solution-state NMR spectroscopy to measure transverse proton relaxation rates for methyl groups in folded ribosome-nascent chain complexes of the FLN5 filamin domain. We observe substantial increases in relaxation rates for the nascent chain relative to the isolated domain, which can be related to changes in effective rotational correlation times using measurements of relaxation and cross-correlated relaxation in the isolated domain. Using this approach, we can identify interactions between the nascent chain and the ribosome surface, driven predominantly by electrostatics, and by measuring the change in these interactions as the subsequent FLN6 domain emerges, we may deduce their impact on the free energy landscapes associated with the co-translational folding process.
NMR measurements of methyl relaxation in translationally-arrested ribosome-nascent chain complexes probe the dynamics of folded nascent polypeptides emerging during biosynthesis and quantify their interaction with the ribosome surface. |
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NMR measurements of methyl relaxation in translationally-arrested ribosome-nascent chain complexes probe the dynamics of folded nascent polypeptides emerging during biosynthesis and quantify their interaction with the ribosome surface.</description><identifier>ISSN: 2041-6520</identifier><identifier>EISSN: 2041-6539</identifier><identifier>DOI: 10.1039/d1sc04313g</identifier><identifier>PMID: 34745542</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Biosynthesis ; Chain dynamics ; Chemistry ; Domains ; Electrostatics ; Folding ; Free energy ; NMR spectroscopy ; Perturbation ; Spectrum analysis</subject><ispartof>Chemical science (Cambridge), 2021-10, Vol.12 (39), p.1312-13126</ispartof><rights>This journal is © The Royal Society of Chemistry.</rights><rights>Copyright Royal Society of Chemistry 2021</rights><rights>This journal is © The Royal Society of Chemistry 2021 The Royal Society of Chemistry</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-84f4d28b6b8fae9b68286bcc9f8b5b2898aa3dd37caf7d890a38209964c388ae3</citedby><cites>FETCH-LOGICAL-c428t-84f4d28b6b8fae9b68286bcc9f8b5b2898aa3dd37caf7d890a38209964c388ae3</cites><orcidid>0000-0002-6710-3843 ; 0000-0001-7810-3753 ; 0000-0003-2963-8078 ; 0000-0002-6321-4052 ; 0000-0001-6498-334X ; 0000-0003-3963-082X</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/PMC8513902/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513902/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34745542$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Burridge, Charles</creatorcontrib><creatorcontrib>Waudby, Christopher A</creatorcontrib><creatorcontrib>W odarski, Tomasz</creatorcontrib><creatorcontrib>Cassaignau, Anaïs M. E</creatorcontrib><creatorcontrib>Cabrita, Lisa D</creatorcontrib><creatorcontrib>Christodoulou, John</creatorcontrib><title>Nascent chain dynamics and ribosome interactions within folded ribosome-nascent chain complexes observed by NMR spectroscopy</title><title>Chemical science (Cambridge)</title><addtitle>Chem Sci</addtitle><description>The folding of many proteins can begin during biosynthesis on the ribosome and can be modulated by the ribosome itself. Such perturbations are generally believed to be mediated through interactions between the nascent chain and the ribosome surface, but despite recent progress in characterising interactions of unfolded states with the ribosome, and their impact on the initiation of co-translational folding, a complete quantitative analysis of interactions across both folded and unfolded states of a nascent chain has yet to be realised. Here we apply solution-state NMR spectroscopy to measure transverse proton relaxation rates for methyl groups in folded ribosome-nascent chain complexes of the FLN5 filamin domain. We observe substantial increases in relaxation rates for the nascent chain relative to the isolated domain, which can be related to changes in effective rotational correlation times using measurements of relaxation and cross-correlated relaxation in the isolated domain. Using this approach, we can identify interactions between the nascent chain and the ribosome surface, driven predominantly by electrostatics, and by measuring the change in these interactions as the subsequent FLN6 domain emerges, we may deduce their impact on the free energy landscapes associated with the co-translational folding process.
NMR measurements of methyl relaxation in translationally-arrested ribosome-nascent chain complexes probe the dynamics of folded nascent polypeptides emerging during biosynthesis and quantify their interaction with the ribosome surface.</description><subject>Biosynthesis</subject><subject>Chain dynamics</subject><subject>Chemistry</subject><subject>Domains</subject><subject>Electrostatics</subject><subject>Folding</subject><subject>Free energy</subject><subject>NMR spectroscopy</subject><subject>Perturbation</subject><subject>Spectrum analysis</subject><issn>2041-6520</issn><issn>2041-6539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNpd0ttLHDEUB-BQKlXUl75XAn0pwtjcZjZ5Ecp6BbXQy3PIbdzITDIms6sL_vFGV9favCSQjx_n5ASAzxgdYETFd4uzQYxiev0BbBHEcNXUVHxcnwnaBLs536CyKMU1mXwCm5RNWF0zsgUerlQ2LozQzJQP0C6D6r3JUAULk9cxx95BH0aXlBl9DBne-XFWZBs7695MFd7lmNgPnbt3GUadXVoUqZfw6vIXzIMzY4rZxGG5AzZa1WW3-7Jvg78nx3-mZ9XFz9Pz6Y-LyjDCx4qzllnCdaN5q5zQDSe80caIlutaEy64UtRaOjGqnVgukKKcICEaZijnytFtcLjKHea6d_apzqQ6OSTfq7SUUXn5_ib4mbyOC8lrTAUiJeDbS0CKt3OXR9n70m7XqeDiPEtSixrjBjWo0K__0Zs4T6G0VxTHjJOGiaL2V8qUp8jJtetiMJJPc5VH-Pf0ea6nBe_9W_6avk6xgC8rkLJZ3759DPoIF9Wqvw</recordid><startdate>20211013</startdate><enddate>20211013</enddate><creator>Burridge, Charles</creator><creator>Waudby, Christopher A</creator><creator>W odarski, Tomasz</creator><creator>Cassaignau, Anaïs M. E</creator><creator>Cabrita, Lisa D</creator><creator>Christodoulou, John</creator><general>Royal Society of Chemistry</general><general>The Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6710-3843</orcidid><orcidid>https://orcid.org/0000-0001-7810-3753</orcidid><orcidid>https://orcid.org/0000-0003-2963-8078</orcidid><orcidid>https://orcid.org/0000-0002-6321-4052</orcidid><orcidid>https://orcid.org/0000-0001-6498-334X</orcidid><orcidid>https://orcid.org/0000-0003-3963-082X</orcidid></search><sort><creationdate>20211013</creationdate><title>Nascent chain dynamics and ribosome interactions within folded ribosome-nascent chain complexes observed by NMR spectroscopy</title><author>Burridge, Charles ; Waudby, Christopher A ; W odarski, Tomasz ; Cassaignau, Anaïs M. 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E</creatorcontrib><creatorcontrib>Cabrita, Lisa D</creatorcontrib><creatorcontrib>Christodoulou, John</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Chemical science (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Burridge, Charles</au><au>Waudby, Christopher A</au><au>W odarski, Tomasz</au><au>Cassaignau, Anaïs M. E</au><au>Cabrita, Lisa D</au><au>Christodoulou, John</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nascent chain dynamics and ribosome interactions within folded ribosome-nascent chain complexes observed by NMR spectroscopy</atitle><jtitle>Chemical science (Cambridge)</jtitle><addtitle>Chem Sci</addtitle><date>2021-10-13</date><risdate>2021</risdate><volume>12</volume><issue>39</issue><spage>1312</spage><epage>13126</epage><pages>1312-13126</pages><issn>2041-6520</issn><eissn>2041-6539</eissn><abstract>The folding of many proteins can begin during biosynthesis on the ribosome and can be modulated by the ribosome itself. Such perturbations are generally believed to be mediated through interactions between the nascent chain and the ribosome surface, but despite recent progress in characterising interactions of unfolded states with the ribosome, and their impact on the initiation of co-translational folding, a complete quantitative analysis of interactions across both folded and unfolded states of a nascent chain has yet to be realised. Here we apply solution-state NMR spectroscopy to measure transverse proton relaxation rates for methyl groups in folded ribosome-nascent chain complexes of the FLN5 filamin domain. We observe substantial increases in relaxation rates for the nascent chain relative to the isolated domain, which can be related to changes in effective rotational correlation times using measurements of relaxation and cross-correlated relaxation in the isolated domain. Using this approach, we can identify interactions between the nascent chain and the ribosome surface, driven predominantly by electrostatics, and by measuring the change in these interactions as the subsequent FLN6 domain emerges, we may deduce their impact on the free energy landscapes associated with the co-translational folding process.
NMR measurements of methyl relaxation in translationally-arrested ribosome-nascent chain complexes probe the dynamics of folded nascent polypeptides emerging during biosynthesis and quantify their interaction with the ribosome surface.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>34745542</pmid><doi>10.1039/d1sc04313g</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-6710-3843</orcidid><orcidid>https://orcid.org/0000-0001-7810-3753</orcidid><orcidid>https://orcid.org/0000-0003-2963-8078</orcidid><orcidid>https://orcid.org/0000-0002-6321-4052</orcidid><orcidid>https://orcid.org/0000-0001-6498-334X</orcidid><orcidid>https://orcid.org/0000-0003-3963-082X</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Biosynthesis Chain dynamics Chemistry Domains Electrostatics Folding Free energy NMR spectroscopy Perturbation Spectrum analysis |
title | Nascent chain dynamics and ribosome interactions within folded ribosome-nascent chain complexes observed by NMR spectroscopy |
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