Cadherin Mechanics and Complexation: The Importance of Calcium Binding
E-cadherins belong to a family of membrane-bound, cellular adhesion proteins. Their adhesive properties mainly involve the two N-terminal extracellular domains (EC1 and EC2). The junctions between these domains are characterized by calcium ion binding sites, and calcium ions are essential for the co...
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| Veröffentlicht in: | Biophysical journal 2005-12, Vol.89 (6), p.3895-3903 |
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| creator | Cailliez, Fabien Lavery, Richard |
| description | E-cadherins belong to a family of membrane-bound, cellular adhesion proteins. Their adhesive properties mainly involve the two N-terminal extracellular domains (EC1 and EC2). The junctions between these domains are characterized by calcium ion binding sites, and calcium ions are essential for the correct functioning of E-cadherins. Calcium is believed to rigidify the extracellular portion of the protein, which, when complexed, adopts a rod-like conformation. Here, we use molecular dynamics simulations to investigate the dynamics of the EC1-2 portion of E-cadherin in the presence and in the absence of calcium ions. These simulations confirm that
apo-cadherin shows much higher conformational flexibility on a nanosecond timescale than the calcium-bound form. It is also shown that although the
apo-cadherin fragment can spontaneously complex potassium, these monovalent ions are incapable of rigidifying the interdomain junctions. In contrast, removal of the most solvent-exposed calcium ion at the EC1-2 junction does not significantly perturb the dynamical behavior of the fragment. We have also extended this study to the
cis-dimer formed from two EC1-2 fragments, potentially involved in cellular adhesion. Here again, it is shown that the presence of calcium is an important factor in both rigidifying and stabilizing the complex. |
| doi_str_mv | 10.1529/biophysj.105.067322 |
| format | Article |
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apo-cadherin shows much higher conformational flexibility on a nanosecond timescale than the calcium-bound form. It is also shown that although the
apo-cadherin fragment can spontaneously complex potassium, these monovalent ions are incapable of rigidifying the interdomain junctions. In contrast, removal of the most solvent-exposed calcium ion at the EC1-2 junction does not significantly perturb the dynamical behavior of the fragment. We have also extended this study to the
cis-dimer formed from two EC1-2 fragments, potentially involved in cellular adhesion. Here again, it is shown that the presence of calcium is an important factor in both rigidifying and stabilizing the complex.</description><identifier>ISSN: 0006-3495</identifier><identifier>EISSN: 1542-0086</identifier><identifier>DOI: 10.1529/biophysj.105.067322</identifier><identifier>PMID: 16183887</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Binding Sites ; Biochemistry, Molecular Biology ; Biophysical Theory and Modeling ; Cadherins - chemistry ; Calcium ; Calcium - chemistry ; Cell adhesion & migration ; Computer Simulation ; Kinetics ; Life Sciences ; Mechanics ; Models, Chemical ; Models, Molecular ; Molecular Conformation ; Motion ; Protein Binding ; Protein Structure, Tertiary ; Proteins ; Studies</subject><ispartof>Biophysical journal, 2005-12, Vol.89 (6), p.3895-3903</ispartof><rights>2005 The Biophysical Society</rights><rights>Copyright Biophysical Society Dec 2005</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright © 2005, Biophysical Society 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c584t-ed6ae05ae26b99404ac09d75e3ddae6032600981a2e4b3646c32b85b15f104bb3</citedby><cites>FETCH-LOGICAL-c584t-ed6ae05ae26b99404ac09d75e3ddae6032600981a2e4b3646c32b85b15f104bb3</cites><orcidid>0000-0002-4415-0348</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/PMC1366956/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006349505730320$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,3537,27901,27902,53766,53768,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16183887$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00313392$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Cailliez, Fabien</creatorcontrib><creatorcontrib>Lavery, Richard</creatorcontrib><title>Cadherin Mechanics and Complexation: The Importance of Calcium Binding</title><title>Biophysical journal</title><addtitle>Biophys J</addtitle><description>E-cadherins belong to a family of membrane-bound, cellular adhesion proteins. Their adhesive properties mainly involve the two N-terminal extracellular domains (EC1 and EC2). The junctions between these domains are characterized by calcium ion binding sites, and calcium ions are essential for the correct functioning of E-cadherins. Calcium is believed to rigidify the extracellular portion of the protein, which, when complexed, adopts a rod-like conformation. Here, we use molecular dynamics simulations to investigate the dynamics of the EC1-2 portion of E-cadherin in the presence and in the absence of calcium ions. These simulations confirm that
apo-cadherin shows much higher conformational flexibility on a nanosecond timescale than the calcium-bound form. It is also shown that although the
apo-cadherin fragment can spontaneously complex potassium, these monovalent ions are incapable of rigidifying the interdomain junctions. In contrast, removal of the most solvent-exposed calcium ion at the EC1-2 junction does not significantly perturb the dynamical behavior of the fragment. We have also extended this study to the
cis-dimer formed from two EC1-2 fragments, potentially involved in cellular adhesion. Here again, it is shown that the presence of calcium is an important factor in both rigidifying and stabilizing the complex.</description><subject>Binding Sites</subject><subject>Biochemistry, Molecular Biology</subject><subject>Biophysical Theory and Modeling</subject><subject>Cadherins - chemistry</subject><subject>Calcium</subject><subject>Calcium - chemistry</subject><subject>Cell adhesion & migration</subject><subject>Computer Simulation</subject><subject>Kinetics</subject><subject>Life Sciences</subject><subject>Mechanics</subject><subject>Models, Chemical</subject><subject>Models, Molecular</subject><subject>Molecular Conformation</subject><subject>Motion</subject><subject>Protein Binding</subject><subject>Protein Structure, Tertiary</subject><subject>Proteins</subject><subject>Studies</subject><issn>0006-3495</issn><issn>1542-0086</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kU9v1DAQxSMEokvhEyChiANSD1nGdux1kIrURpRWWsSlnC3HmW28SuxgJyv67XGV5V8PnCyNf-89zbwse01gTTit3jfWj9193K8J8DWIDaP0SbYivKQFgBRPsxUAiIKVFT_JXsS4ByCUA3menRBBJJNys8quat12GKzLv6DptLMm5tq1ee2HsccferLefchvO8xvhtGHSTuDud_lte6NnYf80rrWuruX2bOd7iO-Or6n2berT7f1dbH9-vmmvtgWhstyKrAVGoFrpKKpqhJKbaBqNxxZ22oUwKgAqCTRFMuGiVIYRhvJG8J3BMqmYafZx8V3nJsBW4NuCrpXY7CDDvfKa6v-_XG2U3f-oAgTouIiGZwtBt0j2fXFVj3MABhhrKIHkth3x7Dgv88YJzXYaLDvtUM_RyWk5EBllcC3j8C9n4NLh1CU8A2wtFOC2AKZ4GMMuPsdT0A9FKp-FZoGXC2FJtWbvxf-ozk2mIDzBcB09oPFoKKxmFpqbUAzqdbb_wb8BJJism8</recordid><startdate>20051201</startdate><enddate>20051201</enddate><creator>Cailliez, Fabien</creator><creator>Lavery, Richard</creator><general>Elsevier Inc</general><general>Biophysical Society</general><scope>6I.</scope><scope>AAFTH</scope><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>3V.</scope><scope>7QO</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope><scope>1XC</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4415-0348</orcidid></search><sort><creationdate>20051201</creationdate><title>Cadherin Mechanics and Complexation: The Importance of Calcium Binding</title><author>Cailliez, Fabien ; Lavery, Richard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c584t-ed6ae05ae26b99404ac09d75e3ddae6032600981a2e4b3646c32b85b15f104bb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Binding Sites</topic><topic>Biochemistry, Molecular Biology</topic><topic>Biophysical Theory and Modeling</topic><topic>Cadherins - chemistry</topic><topic>Calcium</topic><topic>Calcium - chemistry</topic><topic>Cell adhesion & migration</topic><topic>Computer Simulation</topic><topic>Kinetics</topic><topic>Life Sciences</topic><topic>Mechanics</topic><topic>Models, Chemical</topic><topic>Models, Molecular</topic><topic>Molecular Conformation</topic><topic>Motion</topic><topic>Protein Binding</topic><topic>Protein Structure, Tertiary</topic><topic>Proteins</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cailliez, Fabien</creatorcontrib><creatorcontrib>Lavery, Richard</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biophysical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cailliez, Fabien</au><au>Lavery, Richard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cadherin Mechanics and Complexation: The Importance of Calcium Binding</atitle><jtitle>Biophysical journal</jtitle><addtitle>Biophys J</addtitle><date>2005-12-01</date><risdate>2005</risdate><volume>89</volume><issue>6</issue><spage>3895</spage><epage>3903</epage><pages>3895-3903</pages><issn>0006-3495</issn><eissn>1542-0086</eissn><abstract>E-cadherins belong to a family of membrane-bound, cellular adhesion proteins. Their adhesive properties mainly involve the two N-terminal extracellular domains (EC1 and EC2). The junctions between these domains are characterized by calcium ion binding sites, and calcium ions are essential for the correct functioning of E-cadherins. Calcium is believed to rigidify the extracellular portion of the protein, which, when complexed, adopts a rod-like conformation. Here, we use molecular dynamics simulations to investigate the dynamics of the EC1-2 portion of E-cadherin in the presence and in the absence of calcium ions. These simulations confirm that
apo-cadherin shows much higher conformational flexibility on a nanosecond timescale than the calcium-bound form. It is also shown that although the
apo-cadherin fragment can spontaneously complex potassium, these monovalent ions are incapable of rigidifying the interdomain junctions. In contrast, removal of the most solvent-exposed calcium ion at the EC1-2 junction does not significantly perturb the dynamical behavior of the fragment. We have also extended this study to the
cis-dimer formed from two EC1-2 fragments, potentially involved in cellular adhesion. Here again, it is shown that the presence of calcium is an important factor in both rigidifying and stabilizing the complex.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>16183887</pmid><doi>10.1529/biophysj.105.067322</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-4415-0348</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Binding Sites Biochemistry, Molecular Biology Biophysical Theory and Modeling Cadherins - chemistry Calcium Calcium - chemistry Cell adhesion & migration Computer Simulation Kinetics Life Sciences Mechanics Models, Chemical Models, Molecular Molecular Conformation Motion Protein Binding Protein Structure, Tertiary Proteins Studies |
| title | Cadherin Mechanics and Complexation: The Importance of Calcium Binding |
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