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Whereas the structure and function of HA\u2019s ectodomain is known in great detail, similar data for the membrane-anchoring part of the protein are missing. Here, we demonstrate that the transmembrane region of a group 2 HA interacts with cholesterol, the major lipid of the plasma membrane and the defining element of the viral budding site nanodomains of the plasma membrane. The cholesterol binding motif is essential for virus replication. Its partial removal affects various steps of the viral life cycle, such as assembly of new virus particles and their subsequent cell entry via membrane fusion. A cholesterol binding pocket in group 2 HAs might be a promising target for a small lipophilic drug that inactivates the virus.<\/jats:p>","DOI":"10.1128\/jvi.00555-19","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T10:06:54Z","timestamp":1558346814000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["Cholesterol Binding to the Transmembrane Region of a Group 2 Hemagglutinin (HA) of Influenza Virus Is Essential for Virus Replication, Affecting both Virus Assembly and HA Fusion Activity"],"prefix":"10.1128","volume":"93","author":[{"given":"Bodan","family":"Hu","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Virologie, Freie Universit\u00e4t Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris Tina","family":"H\u00f6fer","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Virologie, Freie Universit\u00e4t Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Thiele","sequence":"additional","affiliation":[{"name":"Biochemistry and Cell Biology of Lipids, Life &amp; Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Veit","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Virologie, Freie Universit\u00e4t Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.69.1.531"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399401002447"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.4.2038"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2977"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201108175"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200412058"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2005.09.049"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02104-16"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708066104"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/370606"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12118"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2010.12.003"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/2049-632X.12053"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.10.015"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00333"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.2.425"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90344-1"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.10.6449-6458.2005"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.16.7529-7537.2000"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.11.11.3765"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.72.121801.161504"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200709932"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.77.23.12543-12551.2003"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2016.50"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2015.09.014"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2235620100"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20091388"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00704-08"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M900437200"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.18.5501"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2012.01.002"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2008.05.001"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-90-481-8622-8_9"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00031"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemphyslip.2016.04.006"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemphyslip.2016.05.003"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20141114"},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","unstructured":"Hu B H\u00f6fer CT Thiele C Veit M. 2019. 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