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Here we demonstrate that the membrane-proximal domains of Tie2 mediate homotypic interactions, which occur via intermolecular \u03b2-sheet formation and are necessary for Tie2 activation. The structural analysis suggests that Tie2\/Tie1 heterodimerization occurs by the same mechanism. The crystal structures provide a model for angiopoietin-stimulated Tie2 ectodomain dimerization, clustering, and activation and insights into therapeutic targeting.<\/jats:p>","DOI":"10.1073\/pnas.1616166114","type":"journal-article","created":{"date-parts":[[2017,4,10]],"date-time":"2017-04-10T20:55:27Z","timestamp":1491857727000},"page":"4376-4381","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":100,"title":["Structural basis of Tie2 activation and Tie2\/Tie1 heterodimerization"],"prefix":"10.1073","volume":"114","author":[{"given":"Veli-Matti","family":"Lepp\u00e4nen","sequence":"first","affiliation":[{"name":"Wihuri Research Institute, Biomedicum Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pipsa","family":"Saharinen","sequence":"additional","affiliation":[{"name":"Wihuri Research Institute, Biomedicum Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland;"},{"name":"Translational Cancer Biology Program, Research Programs Unit, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Alitalo","sequence":"additional","affiliation":[{"name":"Wihuri Research Institute, Biomedicum Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland;"},{"name":"Translational Cancer Biology Program, Research Programs Unit, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2017,4,10]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1146\/annurev-cellbio-092910-154002","article-title":"Developmental and pathological angiogenesis","volume":"27","author":"Chung AS","year":"2011","unstructured":"AS Chung, N Ferrara, Developmental and pathological angiogenesis. 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