{"created":"2023-06-20T13:21:52.055909+00:00","id":2166,"links":{},"metadata":{"_buckets":{"deposit":"eb5ff165-f8f0-424d-9005-60dc2387610a"},"_deposit":{"created_by":21,"id":"2166","owners":[21],"pid":{"revision_id":0,"type":"depid","value":"2166"},"status":"published"},"_oai":{"id":"oai:ir.soken.ac.jp:00002166","sets":["2:428:15"]},"author_link":["0","0","0"],"item_1_creator_2":{"attribute_name":"著者名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"ROHAIM, AHMED MOHSEN AMIN"}],"nameIdentifiers":[{}]}]},"item_1_creator_3":{"attribute_name":"フリガナ","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"ロハイム, アーメッド　モーセン　アミン"}],"nameIdentifiers":[{}]}]},"item_1_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2010-09-30"}]},"item_1_degree_grantor_5":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"総合研究大学院大学"}]}]},"item_1_degree_name_6":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（理学）"}]},"item_1_description_12":{"attribute_name":"要旨","attribute_value_mlt":[{"subitem_description":"Nuclear factor kappa B (NF-<small>K</small>B) is a key mediator of innate and adaptive immune\r\nresponse. lncorrect regulation of NF-<small>K</small>B pathway has been linked to immune and\r\ninflammatory disease as well as cancers. TAX1-binding protein 1 (TAX1BP1) is a\r\nnegative regulator of TNF-alpha- and IL-1β-induced NF-<small>K</small>B activation. TAX1BP1\r\ncomprises two C-terminal zinc finger domains that bind to mono- and polyubiquitin,\r\nwhich are needed for TRAF6 (TNF-associated factor-6) or RIP1 (receptor interacting\r\nprotein-1) association followed by recruitment of A20 deubiquitinase (DUB), resulting in\r\nNF-<small>K</small>B inhibition. TAX1BP1 acts as an adaptor protein, facilitating the process of de-\r\nubiquitination of target protein, resulting in the down regulation of the NF-<small>K</small>B pathway.\r\n\r\nln order to acquire a better understanding of the molecular interaction between the\r\nubiquitin zinc finger binding (UBZ) domain and ubiquitin, TAX1BP1 UBZ domain\r\ninteraction with mono-ubiquitin and different polyubiquitin chains were investigated in\r\nthis study. TAX1BP1 UBZ domain showed remarkable difference in terms of binding\r\naffinities to monoubiquitin and polyubiquitin chains, as data reveals that there is a\r\nsignificantly higher binding affinity to polyubiquitin (linear, lysine 63 and lysine 48\r\nlinked diubiquitin) chains over monoubiquitin.\r\n\r\nThe crystal structure of the C-terminal UBZ domains of TAX1BP1 in fusion with green\r\nFluorescence Protein (GFP) was solved at 2.8 Å resolution. The crystal structure shows\r\ntwo tandem zinc fingers of the classical type C2H2, owing to the zinc coordinating\r\natoms, both having a β-β-α fold. Other members of the same C2H2 UBZ family are\r\nproposed to bind ubiquitin exclusively through the α-helix in a manner similar to the\r\ninverted ubiquitin-interacting motif (IUIM). Superposition of the α-helix of the UBZ\r\ndomain of TAX1BP1 to existing structural models indicates similar conformation of the\r\nubiquitin binding surface. However, through biochemical experiments, a model of\r\nmonoubiquitin/diubiquitin UBZ domain complex is proposed, indicating a new mode of\r\ninteraction between ubiquitin and UBZ domain of TAX1BP1, giving an insight to the\r\nmechanism of ubiquitin recognition by TAX1BP1, and its function in the NF-<small>K</small>B\r\npathway.\r\n\r\nUbiquitin can be assembled in chains; the topology and signaling characteristics of these chains vary depending on the type of the linkage, adding an extra level of complexity in signaling. &quot;Linear&quot; polyubiquitin chain is a type of polyubiquitin assembly found recently, where ubiquitin moieties are threaded head to tail, and not like the classical lysine linked polyubiquitin chains. Linear polyubiquitin plays an indispensible role in the NF-<small>K</small>B pathway. The crystal structure of linear diubiquitin was solved at 1.9 Å resolution,giving a closer understanding of the mechanism of interactions. It is shown that linear diubiquitin can acquire more than one conformation in solution to meet the surface and chemical complementarities of the cognate domains, and also emphasizing the importance of the linker region, between the two ubiquitin moieties which plays a pivotal role in the process of specific recognition.","subitem_description_type":"Other"}]},"item_1_description_7":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"総研大甲第1380号","subitem_description_type":"Other"}]},"item_1_select_14":{"attribute_name":"所蔵","attribute_value_mlt":[{"subitem_select_item":"有"}]},"item_1_select_8":{"attribute_name":"研究科","attribute_value_mlt":[{"subitem_select_item":"高エネルギー加速器科学研究科"}]},"item_1_select_9":{"attribute_name":"専攻","attribute_value_mlt":[{"subitem_select_item":"13 物質構造科学専攻"}]},"item_1_text_10":{"attribute_name":"学位授与年度","attribute_value_mlt":[{"subitem_text_value":"2010"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"ROHAIM, Ahmed Mohsen Amin","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"甲1380_要旨.pdf","filesize":[{"value":"215.0 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"要旨・審査要旨","url":"https://ir.soken.ac.jp/record/2166/files/甲1380_要旨.pdf"},"version_id":"ec3004d6-4b95-45ce-ab91-6d41f77f3e85"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"STRUCTURAL STUDIES OF UBIQUITIN-BINDING ZINC FINGER DOMAINS IN THE NUCLEAR FACTOR KAPPA B PATHWAY","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"STRUCTURAL STUDIES OF UBIQUITIN-BINDING ZINC FINGER DOMAINS IN THE NUCLEAR FACTOR KAPPA B PATHWAY"},{"subitem_title":"STRUCTURAL STUDIES OF UBIQUITIN-BINDING ZINC FINGER DOMAINS IN THE NUCLEAR FACTOR KAPPA B PATHWAY","subitem_title_language":"en"}]},"item_type_id":"1","owner":"21","path":["15"],"pubdate":{"attribute_name":"公開日","attribute_value":"2011-06-03"},"publish_date":"2011-06-03","publish_status":"0","recid":"2166","relation_version_is_last":true,"title":["STRUCTURAL STUDIES OF UBIQUITIN-BINDING ZINC FINGER DOMAINS IN THE NUCLEAR FACTOR KAPPA B PATHWAY"],"weko_creator_id":"21","weko_shared_id":-1},"updated":"2023-06-20T15:55:08.827160+00:00"}