Force regulated conformational change of integrin αVβ3
Integrins mediate cell adhesion to extracellular matrix and transduce signals bidirectionally across the membrane. Integrin αVβ3 has been shown to play an essential role in tumor metastasis, angiogenesis, hemostasis and phagocytosis. Integrins can take several conformations, including the bent and e...
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Veröffentlicht in: | Matrix biology 2017-07, Vol.60-61, p.70-85 |
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creator | Chen, Yunfeng Lee, Hyunjung Tong, Haibin Schwartz, Martin Zhu, Cheng |
description | Integrins mediate cell adhesion to extracellular matrix and transduce signals bidirectionally across the membrane. Integrin αVβ3 has been shown to play an essential role in tumor metastasis, angiogenesis, hemostasis and phagocytosis. Integrins can take several conformations, including the bent and extended conformations of the ectodomain, which regulate integrin functions. Using a biomembrane force probe, we characterized the bending and unbending conformational changes of single αVβ3 integrins on living cell surfaces in real-time. We measured the probabilities of conformational changes, rates and speeds of conformational transitions, and the dynamic equilibrium between the two conformations, which were regulated by tensile force, dependent on the ligand, and altered by point mutations. These findings provide insights into how αVβ3 acts as a molecular machine and how its physiological function and molecular structure are coupled at the single‐molecule level.
•We characterized the bending and unbending conformational changes of a single integrin αVβ3 molecule on a living cell surface in real-time.•The bending and unbending conformational changes are regulated by tensile force, dependent on the ligand, and altered by point mutations.•Our findings provide insights into how the physiological functions and molecular structure of αVβ3 are coupled at the single molecule level. |
doi_str_mv | 10.1016/j.matbio.2016.07.002 |
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•We characterized the bending and unbending conformational changes of a single integrin αVβ3 molecule on a living cell surface in real-time.•The bending and unbending conformational changes are regulated by tensile force, dependent on the ligand, and altered by point mutations.•Our findings provide insights into how the physiological functions and molecular structure of αVβ3 are coupled at the single molecule level.</description><identifier>ISSN: 0945-053X</identifier><identifier>EISSN: 1569-1802</identifier><identifier>DOI: 10.1016/j.matbio.2016.07.002</identifier><identifier>PMID: 27423389</identifier><language>eng</language><publisher>Elsevier B.V</publisher><subject>Binding kinetics ; Biomechanics ; Force regulation ; Integrin conformational change ; Integrin αVβ3</subject><ispartof>Matrix biology, 2017-07, Vol.60-61, p.70-85</ispartof><rights>2016 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3552-e652b53ed2e69d5c6d085d134e81d03a19d434fcea219424847bbc6a1fd7a95d3</citedby><cites>FETCH-LOGICAL-c3552-e652b53ed2e69d5c6d085d134e81d03a19d434fcea219424847bbc6a1fd7a95d3</cites><orcidid>0000-0002-1718-565X ; 0000-0001-7618-107X ; 0000-0002-2071-1243</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.matbio.2016.07.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,781,785,886,3551,27926,27927,45997</link.rule.ids></links><search><creatorcontrib>Chen, Yunfeng</creatorcontrib><creatorcontrib>Lee, Hyunjung</creatorcontrib><creatorcontrib>Tong, Haibin</creatorcontrib><creatorcontrib>Schwartz, Martin</creatorcontrib><creatorcontrib>Zhu, Cheng</creatorcontrib><title>Force regulated conformational change of integrin αVβ3</title><title>Matrix biology</title><description>Integrins mediate cell adhesion to extracellular matrix and transduce signals bidirectionally across the membrane. Integrin αVβ3 has been shown to play an essential role in tumor metastasis, angiogenesis, hemostasis and phagocytosis. Integrins can take several conformations, including the bent and extended conformations of the ectodomain, which regulate integrin functions. Using a biomembrane force probe, we characterized the bending and unbending conformational changes of single αVβ3 integrins on living cell surfaces in real-time. We measured the probabilities of conformational changes, rates and speeds of conformational transitions, and the dynamic equilibrium between the two conformations, which were regulated by tensile force, dependent on the ligand, and altered by point mutations. These findings provide insights into how αVβ3 acts as a molecular machine and how its physiological function and molecular structure are coupled at the single‐molecule level.
•We characterized the bending and unbending conformational changes of a single integrin αVβ3 molecule on a living cell surface in real-time.•The bending and unbending conformational changes are regulated by tensile force, dependent on the ligand, and altered by point mutations.•Our findings provide insights into how the physiological functions and molecular structure of αVβ3 are coupled at the single molecule level.</description><subject>Binding kinetics</subject><subject>Biomechanics</subject><subject>Force regulation</subject><subject>Integrin conformational change</subject><subject>Integrin αVβ3</subject><issn>0945-053X</issn><issn>1569-1802</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp9kM9KAzEQh4MoWqtv4GGPXnbN393sRZBiVRC8qHgL2WS2TdkmmmwFH0sfpM_klhbFi6dhmB_fzHwInRFcEEzKi0Wx1H3jQkGHrsBVgTHdQyMiyjonEtN9NMI1FzkW7OUIHae0wBhzXslDdEQrThmT9QjJaYgGsgizVad7sJkJvg1xQLvgdZeZufYzyEKbOd_DLDqfrT-f11_sBB20uktwuqtj9DS9fpzc5vcPN3eTq_vcMCFoDqWgjWBgKZS1Faa0WApLGAdJLGaa1JYz3hrQlNSccsmrpjGlJq2tdC0sG6PLLfd11SzBGvB91J16jW6p44cK2qm_E-_mahbelaBs-FIOgPMdIIa3FaReLV0y0HXaQ1glRSQtqyFb0iHKt1ETQ0oR2p81BKuNdLVQW-lqI13hSg3Sf0-EwcO7g6iSceANWBfB9MoG9z_gG3KBjRU</recordid><startdate>20170701</startdate><enddate>20170701</enddate><creator>Chen, Yunfeng</creator><creator>Lee, Hyunjung</creator><creator>Tong, Haibin</creator><creator>Schwartz, Martin</creator><creator>Zhu, Cheng</creator><general>Elsevier B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1718-565X</orcidid><orcidid>https://orcid.org/0000-0001-7618-107X</orcidid><orcidid>https://orcid.org/0000-0002-2071-1243</orcidid></search><sort><creationdate>20170701</creationdate><title>Force regulated conformational change of integrin αVβ3</title><author>Chen, Yunfeng ; Lee, Hyunjung ; Tong, Haibin ; Schwartz, Martin ; Zhu, Cheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3552-e652b53ed2e69d5c6d085d134e81d03a19d434fcea219424847bbc6a1fd7a95d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Binding kinetics</topic><topic>Biomechanics</topic><topic>Force regulation</topic><topic>Integrin conformational change</topic><topic>Integrin αVβ3</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Yunfeng</creatorcontrib><creatorcontrib>Lee, Hyunjung</creatorcontrib><creatorcontrib>Tong, Haibin</creatorcontrib><creatorcontrib>Schwartz, Martin</creatorcontrib><creatorcontrib>Zhu, Cheng</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Matrix biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Yunfeng</au><au>Lee, Hyunjung</au><au>Tong, Haibin</au><au>Schwartz, Martin</au><au>Zhu, Cheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Force regulated conformational change of integrin αVβ3</atitle><jtitle>Matrix biology</jtitle><date>2017-07-01</date><risdate>2017</risdate><volume>60-61</volume><spage>70</spage><epage>85</epage><pages>70-85</pages><issn>0945-053X</issn><eissn>1569-1802</eissn><abstract>Integrins mediate cell adhesion to extracellular matrix and transduce signals bidirectionally across the membrane. Integrin αVβ3 has been shown to play an essential role in tumor metastasis, angiogenesis, hemostasis and phagocytosis. Integrins can take several conformations, including the bent and extended conformations of the ectodomain, which regulate integrin functions. Using a biomembrane force probe, we characterized the bending and unbending conformational changes of single αVβ3 integrins on living cell surfaces in real-time. We measured the probabilities of conformational changes, rates and speeds of conformational transitions, and the dynamic equilibrium between the two conformations, which were regulated by tensile force, dependent on the ligand, and altered by point mutations. These findings provide insights into how αVβ3 acts as a molecular machine and how its physiological function and molecular structure are coupled at the single‐molecule level.
•We characterized the bending and unbending conformational changes of a single integrin αVβ3 molecule on a living cell surface in real-time.•The bending and unbending conformational changes are regulated by tensile force, dependent on the ligand, and altered by point mutations.•Our findings provide insights into how the physiological functions and molecular structure of αVβ3 are coupled at the single molecule level.</abstract><pub>Elsevier B.V</pub><pmid>27423389</pmid><doi>10.1016/j.matbio.2016.07.002</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-1718-565X</orcidid><orcidid>https://orcid.org/0000-0001-7618-107X</orcidid><orcidid>https://orcid.org/0000-0002-2071-1243</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Binding kinetics Biomechanics Force regulation Integrin conformational change Integrin αVβ3 |
title | Force regulated conformational change of integrin αVβ3 |
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