Molecular basis of a redox switch: molecular dynamics simulations and surface plasmon resonance provide insight into reduced and oxidised angiotensinogen
Angiotensinogen fine-tunes the tightly controlled activity of the renin-angiotensin system by modulating the release of angiotensin peptides that control blood pressure. One mechanism by which this modulation is achieved is via angiotensinogen's Cys18-Cys138 disulfide bond that acts as a redox...
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| Veröffentlicht in: | Biochemical journal 2021-09, Vol.478 (17), p.3319-3330 |
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| creator | Crowther, Jennifer M Gilmour, Letitia H Porebski, Benjamin T Heath, Sarah G Pattinson, Neil R Owen, Maurice C Fredericks, Rayleen Buckle, Ashley M Fee, Conan J Göbl, Christoph Dobson, Renwick C J |
| description | Angiotensinogen fine-tunes the tightly controlled activity of the renin-angiotensin system by modulating the release of angiotensin peptides that control blood pressure. One mechanism by which this modulation is achieved is via angiotensinogen's Cys18-Cys138 disulfide bond that acts as a redox switch. Molecular dynamics simulations of each redox state of angiotensinogen reveal subtle dynamic differences between the reduced and oxidised forms, particularly at the N-terminus. Surface plasmon resonance data demonstrate that the two redox forms of angiotensinogen display different binding kinetics to an immobilised anti-angiotensinogen monoclonal antibody. Mass spectrometry mapped the epitope for the antibody to the N-terminal region of angiotensinogen. We therefore provide evidence that the different redox forms of angiotensinogen can be detected by an antibody-based detection method. |
| doi_str_mv | 10.1042/BCJ20210476 |
| format | Article |
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One mechanism by which this modulation is achieved is via angiotensinogen's Cys18-Cys138 disulfide bond that acts as a redox switch. Molecular dynamics simulations of each redox state of angiotensinogen reveal subtle dynamic differences between the reduced and oxidised forms, particularly at the N-terminus. Surface plasmon resonance data demonstrate that the two redox forms of angiotensinogen display different binding kinetics to an immobilised anti-angiotensinogen monoclonal antibody. Mass spectrometry mapped the epitope for the antibody to the N-terminal region of angiotensinogen. We therefore provide evidence that the different redox forms of angiotensinogen can be detected by an antibody-based detection method.</description><identifier>ISSN: 0264-6021</identifier><identifier>EISSN: 1470-8728</identifier><identifier>DOI: 10.1042/BCJ20210476</identifier><identifier>PMID: 34424335</identifier><language>eng</language><publisher>England</publisher><subject>Angiotensinogen - chemistry ; Angiotensinogen - genetics ; Angiotensinogen - immunology ; Angiotensinogen - metabolism ; Antibodies, Monoclonal - immunology ; Blood Pressure - physiology ; Cysteine - metabolism ; Disulfides - metabolism ; Epitopes - immunology ; Humans ; Kinetics ; Molecular Dynamics Simulation ; Oxidation-Reduction ; Protein Binding ; Protein Conformation, alpha-Helical ; Recombinant Proteins - isolation & purification ; Recombinant Proteins - metabolism ; Renin-Angiotensin System - physiology ; Surface Plasmon Resonance - methods</subject><ispartof>Biochemical journal, 2021-09, Vol.478 (17), p.3319-3330</ispartof><rights>2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-80b9c355caa7502b2d9aa65be45b5827e913ac96997699377ecec3f79d80eba43</citedby><cites>FETCH-LOGICAL-c381t-80b9c355caa7502b2d9aa65be45b5827e913ac96997699377ecec3f79d80eba43</cites><orcidid>0000-0003-1398-0442 ; 0000-0002-9670-2204 ; 0000-0002-5506-4939</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/PMC7612104/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612104/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,3266,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34424335$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Crowther, Jennifer M</creatorcontrib><creatorcontrib>Gilmour, Letitia H</creatorcontrib><creatorcontrib>Porebski, Benjamin T</creatorcontrib><creatorcontrib>Heath, Sarah G</creatorcontrib><creatorcontrib>Pattinson, Neil R</creatorcontrib><creatorcontrib>Owen, Maurice C</creatorcontrib><creatorcontrib>Fredericks, Rayleen</creatorcontrib><creatorcontrib>Buckle, Ashley M</creatorcontrib><creatorcontrib>Fee, Conan J</creatorcontrib><creatorcontrib>Göbl, Christoph</creatorcontrib><creatorcontrib>Dobson, Renwick C J</creatorcontrib><title>Molecular basis of a redox switch: molecular dynamics simulations and surface plasmon resonance provide insight into reduced and oxidised angiotensinogen</title><title>Biochemical journal</title><addtitle>Biochem J</addtitle><description>Angiotensinogen fine-tunes the tightly controlled activity of the renin-angiotensin system by modulating the release of angiotensin peptides that control blood pressure. One mechanism by which this modulation is achieved is via angiotensinogen's Cys18-Cys138 disulfide bond that acts as a redox switch. Molecular dynamics simulations of each redox state of angiotensinogen reveal subtle dynamic differences between the reduced and oxidised forms, particularly at the N-terminus. Surface plasmon resonance data demonstrate that the two redox forms of angiotensinogen display different binding kinetics to an immobilised anti-angiotensinogen monoclonal antibody. Mass spectrometry mapped the epitope for the antibody to the N-terminal region of angiotensinogen. We therefore provide evidence that the different redox forms of angiotensinogen can be detected by an antibody-based detection method.</description><subject>Angiotensinogen - chemistry</subject><subject>Angiotensinogen - genetics</subject><subject>Angiotensinogen - immunology</subject><subject>Angiotensinogen - metabolism</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Blood Pressure - physiology</subject><subject>Cysteine - metabolism</subject><subject>Disulfides - metabolism</subject><subject>Epitopes - immunology</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Molecular Dynamics Simulation</subject><subject>Oxidation-Reduction</subject><subject>Protein Binding</subject><subject>Protein Conformation, alpha-Helical</subject><subject>Recombinant Proteins - isolation & purification</subject><subject>Recombinant Proteins - metabolism</subject><subject>Renin-Angiotensin System - physiology</subject><subject>Surface Plasmon Resonance - methods</subject><issn>0264-6021</issn><issn>1470-8728</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1v1DAQhi1ERbeFE3fkIxIK-CtxwgEJVhSoirjAOZo4k12jxF48SWl_Cv-23ras2oM19swzr0fzMvZSirdSGPXu0_pcCZWvtnrCVtJYUdRW1U_ZSqjKFFWuHbMTot9CSCOMeMaOtTHKaF2u2L_vcUS3jJB4B-SJx4EDT9jHK05__ey27_l0QPrrAJN3xMlPOTH7GIhD6DktaQCHfDcCTTFkAYoBwj6T4qXvkftAfrOdc5zjXn9x2N-2xivfe7p9bHycMXMhbjA8Z0cDjIQv7uMp-3X2-ef6a3Hx48u39ceLwulazkUtusbpsnQAthSqU30DUJUdmrIra2WxkRpcUzWNzUdbiw6dHmzT1wI7MPqUfbjT3S3dhL3DMCcY213yE6TrNoJvH1eC37abeNnaSu63ngVe3wuk-GdBmtvJk8NxhIBxoVaVlbbSNpXI6Js71KVIlHA4fCNFuzezfWBmpl89nOzA_ndP3wBqz58E</recordid><startdate>20210917</startdate><enddate>20210917</enddate><creator>Crowther, Jennifer M</creator><creator>Gilmour, Letitia H</creator><creator>Porebski, Benjamin T</creator><creator>Heath, Sarah G</creator><creator>Pattinson, Neil R</creator><creator>Owen, Maurice C</creator><creator>Fredericks, Rayleen</creator><creator>Buckle, Ashley M</creator><creator>Fee, Conan J</creator><creator>Göbl, Christoph</creator><creator>Dobson, Renwick C J</creator><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/0000-0003-1398-0442</orcidid><orcidid>https://orcid.org/0000-0002-9670-2204</orcidid><orcidid>https://orcid.org/0000-0002-5506-4939</orcidid></search><sort><creationdate>20210917</creationdate><title>Molecular basis of a redox switch: molecular dynamics simulations and surface plasmon resonance provide insight into reduced and oxidised angiotensinogen</title><author>Crowther, Jennifer M ; Gilmour, Letitia H ; Porebski, Benjamin T ; Heath, Sarah G ; Pattinson, Neil R ; Owen, Maurice C ; Fredericks, Rayleen ; Buckle, Ashley M ; Fee, Conan J ; Göbl, Christoph ; Dobson, Renwick C J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-80b9c355caa7502b2d9aa65be45b5827e913ac96997699377ecec3f79d80eba43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Angiotensinogen - chemistry</topic><topic>Angiotensinogen - genetics</topic><topic>Angiotensinogen - immunology</topic><topic>Angiotensinogen - metabolism</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Blood Pressure - physiology</topic><topic>Cysteine - metabolism</topic><topic>Disulfides - metabolism</topic><topic>Epitopes - immunology</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Molecular Dynamics Simulation</topic><topic>Oxidation-Reduction</topic><topic>Protein Binding</topic><topic>Protein Conformation, alpha-Helical</topic><topic>Recombinant Proteins - isolation & purification</topic><topic>Recombinant Proteins - metabolism</topic><topic>Renin-Angiotensin System - physiology</topic><topic>Surface Plasmon Resonance - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Crowther, Jennifer M</creatorcontrib><creatorcontrib>Gilmour, Letitia H</creatorcontrib><creatorcontrib>Porebski, Benjamin T</creatorcontrib><creatorcontrib>Heath, Sarah G</creatorcontrib><creatorcontrib>Pattinson, Neil R</creatorcontrib><creatorcontrib>Owen, Maurice C</creatorcontrib><creatorcontrib>Fredericks, Rayleen</creatorcontrib><creatorcontrib>Buckle, Ashley M</creatorcontrib><creatorcontrib>Fee, Conan J</creatorcontrib><creatorcontrib>Göbl, Christoph</creatorcontrib><creatorcontrib>Dobson, Renwick C J</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>Biochemical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Crowther, Jennifer M</au><au>Gilmour, Letitia H</au><au>Porebski, Benjamin T</au><au>Heath, Sarah G</au><au>Pattinson, Neil R</au><au>Owen, Maurice C</au><au>Fredericks, Rayleen</au><au>Buckle, Ashley M</au><au>Fee, Conan J</au><au>Göbl, Christoph</au><au>Dobson, Renwick C J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular basis of a redox switch: molecular dynamics simulations and surface plasmon resonance provide insight into reduced and oxidised angiotensinogen</atitle><jtitle>Biochemical journal</jtitle><addtitle>Biochem J</addtitle><date>2021-09-17</date><risdate>2021</risdate><volume>478</volume><issue>17</issue><spage>3319</spage><epage>3330</epage><pages>3319-3330</pages><issn>0264-6021</issn><eissn>1470-8728</eissn><abstract>Angiotensinogen fine-tunes the tightly controlled activity of the renin-angiotensin system by modulating the release of angiotensin peptides that control blood pressure. One mechanism by which this modulation is achieved is via angiotensinogen's Cys18-Cys138 disulfide bond that acts as a redox switch. Molecular dynamics simulations of each redox state of angiotensinogen reveal subtle dynamic differences between the reduced and oxidised forms, particularly at the N-terminus. Surface plasmon resonance data demonstrate that the two redox forms of angiotensinogen display different binding kinetics to an immobilised anti-angiotensinogen monoclonal antibody. Mass spectrometry mapped the epitope for the antibody to the N-terminal region of angiotensinogen. 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| subjects | Angiotensinogen - chemistry Angiotensinogen - genetics Angiotensinogen - immunology Angiotensinogen - metabolism Antibodies, Monoclonal - immunology Blood Pressure - physiology Cysteine - metabolism Disulfides - metabolism Epitopes - immunology Humans Kinetics Molecular Dynamics Simulation Oxidation-Reduction Protein Binding Protein Conformation, alpha-Helical Recombinant Proteins - isolation & purification Recombinant Proteins - metabolism Renin-Angiotensin System - physiology Surface Plasmon Resonance - methods |
| title | Molecular basis of a redox switch: molecular dynamics simulations and surface plasmon resonance provide insight into reduced and oxidised angiotensinogen |
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