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Though observed in studies with recombinant domains, whether such quaternary states are present in native Hsp90s is unknown. In this study, native subunit interactions in GRP94, the endoplasmic reticulum Hsp90, were analyzed using chemical cross\u2010linking in conjunction with tandem mass spectrometry. We report the identification of two distinct intermolecular interaction sites. Consistent with previous studies, one site comprises the C\u2010terminal dimerization domain. The remaining site represents a novel intermolecular contact between the N\u2010terminal and middle (M) domains of opposing subunits. This N+M domain interaction was present in the nucleotide\u2010empty, ADP\u2010, ATP\u2010, or geldanamycin\u2010bound states and could be selectively disrupted upon addition of synthetic geldanamycin dimers. These results identify a compact, intertwined quaternary conformation of native GRP94 and suggest that intersubunit N+M interactions are integral to the structural biology of Hsp90.<\/jats:p>","DOI":"10.1110\/ps.052065106","type":"journal-article","created":{"date-parts":[[2006,5,27]],"date-time":"2006-05-27T00:18:54Z","timestamp":1148689134000},"page":"1260-1269","source":"Crossref","is-referenced-by-count":33,"title":["Identification of novel quaternary domain interactions in the Hsp90 chaperone, GRP94"],"prefix":"10.1002","volume":"15","author":[{"given":"Feixia","family":"Chu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason C.","family":"Maynard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Chiosis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher V.","family":"Nicchitta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma L.","family":"Burlingame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi034602h"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/scdb.1999.0320"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(03)00721-6"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301101200"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.9.9.3919"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1084183"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.220430297"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2006.03.092"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407456101"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biophys.30.1.67"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1118370"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(98)00013-8"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0206715"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2410435"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.1144"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M503761200"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5360.69"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083917"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(99)01503-0"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.38.23843"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.25.17525"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2004.03.020"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2004.12.018"},{"key":"e_1_2_6_25_1","doi-asserted-by":"crossref","first-page":"19898","DOI":"10.1016\/S0021-9258(19)47195-0","article-title":"Purification and characterization of the adenosine A2\u2010like binding site from human placental membrane","volume":"264","author":"Hutchison K.A.","year":"1989","journal-title":"J. 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