{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T23:27:51Z","timestamp":1788132471554,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,11,19]],"date-time":"2012-11-19T00:00:00Z","timestamp":1353283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["R15AI094483-01"],"award-info":[{"award-number":["R15AI094483-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>As a target of antiviral drugs, the influenza A M2 protein has been the focus of numerous structural studies and has been extensively explored as a model ion channel. In this study, we capitalize on the expanding body of high\u2010resolution structural data available for the M2 protein to design and interpret site\u2010directed spin\u2010labeling electron paramagnetic resonance spectroscopy experiments on drug\u2010induced conformational changes of the M2 protein embedded in lipid bilayers. We obtained data in the presence of adamantane drugs for two different M2 constructs (M2TM 22\u201346 and M2TMC 23\u201360). M2TM peptides were spin labeled at the <jats:italic>N<\/jats:italic>\u2010terminal end of the transmembrane domain. M2TMC peptides were spin labeled site specifically at cysteine residues substituted for amino acids within the transmembrane domain (L36, I39, I42, and L43) and the <jats:italic>C<\/jats:italic>\u2010terminal amphipathic helix (L46, F47, F48, C50, I51, Y52, R53, F54, F55, and E56). Addition of adamantane drugs brought about significant changes in measured electron paramagnetic resonance spectroscopy environmental parameters consistent with narrowing of the transmembrane channel pore and closer packing of the <jats:italic>C<\/jats:italic>\u2010terminal amphipathic helices.<\/jats:p>","DOI":"10.1002\/pro.2186","type":"journal-article","created":{"date-parts":[[2012,11,8]],"date-time":"2012-11-08T16:31:38Z","timestamp":1352392298000},"page":"65-73","source":"Crossref","is-referenced-by-count":20,"title":["Detection of drug\u2010induced conformational change of a transmembrane protein in lipid bilayers using site\u2010directed spin labeling"],"prefix":"10.1002","volume":"22","author":[{"given":"Jessica L.","family":"Thomaston","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuong A.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily C.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Alice","family":"Upshur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William F.","family":"DeGrado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen P.","family":"Howard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,11,19]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2011.10.009"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00723-009-0079-2"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R500020200"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2010.12.002"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2010.12.003"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja202288m"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.041185805"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi801315m"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2011.09.003"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja202051n"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi901799k"},{"key":"e_1_2_6_13_2","unstructured":"MchaourabHS PerozoE. 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