Protein domain definition should allow for conditional disorder
: Proteins are often classified in a binary fashion as either structured or disordered. However this approach has several deficits. Firstly, protein folding is always conditional on the physiochemical environment. A protein which is structured in some circumstances will be disordered in others. Seco...
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Veröffentlicht in: | Protein science 2013-11, Vol.22 (11), p.1502-1518 |
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description | : Proteins are often classified in a binary fashion as either structured or disordered. However this approach has several deficits. Firstly, protein folding is always conditional on the physiochemical environment. A protein which is structured in some circumstances will be disordered in others. Secondly, it hides a fundamental asymmetry in behavior. While all structured proteins can be unfolded through a change in environment, not all disordered proteins have the capacity for folding. Failure to accommodate these complexities confuses the definition of both protein structural domains and intrinsically disordered regions. We illustrate these points with an experimental study of a family of small binding domains, drawn from the RNA polymerase of mumps virus and its closest relatives. Assessed at face value the domains fall on a structural continuum, with folded, partially folded, and near unstructured members. Yet the disorder present in the family is conditional, and these closely related polypeptides can access the same folded state under appropriate conditions. Any heuristic definition of the protein domain emphasizing conformational stability divides this domain family in two, in a way that makes no biological sense. Structural domains would be better defined by their ability to adopt a specific tertiary structure: a structure that may or may not be realized, dependent on the circumstances. This explicitly allows for the conditional nature of protein folding, and more clearly demarcates structural domains from intrinsically disordered regions that may function without folding.
PDB Code(s): 4KYC
4KYD
4KYE |
doi_str_mv | 10.1002/pro.2336 |
format | Article |
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PDB Code(s): 4KYC
4KYD
4KYE</description><identifier>ISSN: 0961-8368</identifier><identifier>EISSN: 1469-896X</identifier><identifier>DOI: 10.1002/pro.2336</identifier><identifier>PMID: 23963781</identifier><identifier>CODEN: PRCIEI</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Amino Acid Sequence ; coupled binding and folding ; Crystallography, X-Ray ; Evolution, Molecular ; intrinsic protein disorder ; Intrinsically Disordered Proteins - chemistry ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Sequence Data ; mumps virus ; Mumps virus - enzymology ; Phylogeny ; Protein Conformation ; Protein Folding ; Protein Stability ; Protein Structure, Tertiary ; RNA Replicase - chemistry ; RNA Replicase - metabolism ; RNA‐dependent RNA polymerase ; Rubulavirus - chemistry ; rubulaviruses ; stabilizing osmolytes ; trimethylamine N‐oxide ; Viral Proteins - chemistry ; Viral Proteins - metabolism</subject><ispartof>Protein science, 2013-11, Vol.22 (11), p.1502-1518</ispartof><rights>2013 The Protein Society</rights><rights>2013 The Protein Society.</rights><rights>2013 The Protein Society 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4386-d9ab34e08ef4dd25df5086e087e978d2258eea02a14f7146866a25e3625848af3</citedby><cites>FETCH-LOGICAL-c4386-d9ab34e08ef4dd25df5086e087e978d2258eea02a14f7146866a25e3625848af3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831666/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831666/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23963781$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yegambaram, Kavestri</creatorcontrib><creatorcontrib>Bulloch, Esther M.M.</creatorcontrib><creatorcontrib>Kingston, Richard L.</creatorcontrib><title>Protein domain definition should allow for conditional disorder</title><title>Protein science</title><addtitle>Protein Sci</addtitle><description>: Proteins are often classified in a binary fashion as either structured or disordered. However this approach has several deficits. Firstly, protein folding is always conditional on the physiochemical environment. A protein which is structured in some circumstances will be disordered in others. Secondly, it hides a fundamental asymmetry in behavior. While all structured proteins can be unfolded through a change in environment, not all disordered proteins have the capacity for folding. Failure to accommodate these complexities confuses the definition of both protein structural domains and intrinsically disordered regions. We illustrate these points with an experimental study of a family of small binding domains, drawn from the RNA polymerase of mumps virus and its closest relatives. Assessed at face value the domains fall on a structural continuum, with folded, partially folded, and near unstructured members. Yet the disorder present in the family is conditional, and these closely related polypeptides can access the same folded state under appropriate conditions. Any heuristic definition of the protein domain emphasizing conformational stability divides this domain family in two, in a way that makes no biological sense. Structural domains would be better defined by their ability to adopt a specific tertiary structure: a structure that may or may not be realized, dependent on the circumstances. This explicitly allows for the conditional nature of protein folding, and more clearly demarcates structural domains from intrinsically disordered regions that may function without folding.
PDB Code(s): 4KYC
4KYD
4KYE</description><subject>Amino Acid Sequence</subject><subject>coupled binding and folding</subject><subject>Crystallography, X-Ray</subject><subject>Evolution, Molecular</subject><subject>intrinsic protein disorder</subject><subject>Intrinsically Disordered Proteins - chemistry</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>mumps virus</subject><subject>Mumps virus - enzymology</subject><subject>Phylogeny</subject><subject>Protein Conformation</subject><subject>Protein Folding</subject><subject>Protein Stability</subject><subject>Protein Structure, Tertiary</subject><subject>RNA Replicase - chemistry</subject><subject>RNA Replicase - metabolism</subject><subject>RNA‐dependent RNA polymerase</subject><subject>Rubulavirus - chemistry</subject><subject>rubulaviruses</subject><subject>stabilizing osmolytes</subject><subject>trimethylamine N‐oxide</subject><subject>Viral Proteins - chemistry</subject><subject>Viral Proteins - metabolism</subject><issn>0961-8368</issn><issn>1469-896X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1LAzEQhoMotlbBXyALXrys5muz2YsixS8otIiCtxA3sxpJNzXpWvz3plalCp6G4X14mOFFaJ_gY4IxPZkFf0wZExuoT7ioclmJh03Ux5UguWRC9tBOjC8YY04o20Y9yirBSkn66GwS_Bxsmxk_1csBjW3t3Po2i8--cybTzvlF1viQ1b41n5F2mbHRBwNhF2012kXY-5oDdH95cTe8zkfjq5vh-SivOZMiN5V-ZBywhIYbQwvTFFiKtJdQldJQWkgAjakmvCnTC1IITQtgIgVc6oYN0OnKO-sep2BqaOdBOzULdqrDu_Laqt9Ja5_Vk39TTDIihEiCoy9B8K8dxLma2liDc7oF30VFOGdVVUgqE3r4B33xXUhfryjGJZFrwjr4GAM0P8cQrJatpN2rZSsJPVg__gf8riEB-QpYWAfv_4rU5Hb8KfwAVZSWjw</recordid><startdate>201311</startdate><enddate>201311</enddate><creator>Yegambaram, Kavestri</creator><creator>Bulloch, Esther M.M.</creator><creator>Kingston, Richard L.</creator><general>Wiley Subscription Services, Inc</general><general>Blackwell Publishing Ltd</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>7QO</scope><scope>7T5</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201311</creationdate><title>Protein domain definition should allow for conditional disorder</title><author>Yegambaram, Kavestri ; Bulloch, Esther M.M. ; Kingston, Richard L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4386-d9ab34e08ef4dd25df5086e087e978d2258eea02a14f7146866a25e3625848af3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Amino Acid Sequence</topic><topic>coupled binding and folding</topic><topic>Crystallography, X-Ray</topic><topic>Evolution, Molecular</topic><topic>intrinsic protein disorder</topic><topic>Intrinsically Disordered Proteins - chemistry</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>mumps virus</topic><topic>Mumps virus - enzymology</topic><topic>Phylogeny</topic><topic>Protein Conformation</topic><topic>Protein Folding</topic><topic>Protein Stability</topic><topic>Protein Structure, Tertiary</topic><topic>RNA Replicase - chemistry</topic><topic>RNA Replicase - metabolism</topic><topic>RNA‐dependent RNA polymerase</topic><topic>Rubulavirus - chemistry</topic><topic>rubulaviruses</topic><topic>stabilizing osmolytes</topic><topic>trimethylamine N‐oxide</topic><topic>Viral Proteins - chemistry</topic><topic>Viral Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yegambaram, Kavestri</creatorcontrib><creatorcontrib>Bulloch, Esther M.M.</creatorcontrib><creatorcontrib>Kingston, Richard L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Protein science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yegambaram, Kavestri</au><au>Bulloch, Esther M.M.</au><au>Kingston, Richard L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protein domain definition should allow for conditional disorder</atitle><jtitle>Protein science</jtitle><addtitle>Protein Sci</addtitle><date>2013-11</date><risdate>2013</risdate><volume>22</volume><issue>11</issue><spage>1502</spage><epage>1518</epage><pages>1502-1518</pages><issn>0961-8368</issn><eissn>1469-896X</eissn><coden>PRCIEI</coden><abstract>: Proteins are often classified in a binary fashion as either structured or disordered. However this approach has several deficits. Firstly, protein folding is always conditional on the physiochemical environment. A protein which is structured in some circumstances will be disordered in others. Secondly, it hides a fundamental asymmetry in behavior. While all structured proteins can be unfolded through a change in environment, not all disordered proteins have the capacity for folding. Failure to accommodate these complexities confuses the definition of both protein structural domains and intrinsically disordered regions. We illustrate these points with an experimental study of a family of small binding domains, drawn from the RNA polymerase of mumps virus and its closest relatives. Assessed at face value the domains fall on a structural continuum, with folded, partially folded, and near unstructured members. Yet the disorder present in the family is conditional, and these closely related polypeptides can access the same folded state under appropriate conditions. Any heuristic definition of the protein domain emphasizing conformational stability divides this domain family in two, in a way that makes no biological sense. Structural domains would be better defined by their ability to adopt a specific tertiary structure: a structure that may or may not be realized, dependent on the circumstances. This explicitly allows for the conditional nature of protein folding, and more clearly demarcates structural domains from intrinsically disordered regions that may function without folding.
PDB Code(s): 4KYC
4KYD
4KYE</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>23963781</pmid><doi>10.1002/pro.2336</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Sequence coupled binding and folding Crystallography, X-Ray Evolution, Molecular intrinsic protein disorder Intrinsically Disordered Proteins - chemistry Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data mumps virus Mumps virus - enzymology Phylogeny Protein Conformation Protein Folding Protein Stability Protein Structure, Tertiary RNA Replicase - chemistry RNA Replicase - metabolism RNA‐dependent RNA polymerase Rubulavirus - chemistry rubulaviruses stabilizing osmolytes trimethylamine N‐oxide Viral Proteins - chemistry Viral Proteins - metabolism |
title | Protein domain definition should allow for conditional disorder |
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