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ツゲ ヒデアキ
TSUGE HIDEAKI
津下 英明 所属 京都産業大学 生命科学部 先端生命科学科 職種 教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2015/08/07 |
| 形態種別 | 研究論文 |
| 査読 | 査読あり |
| 標題 | Rho GTPase Recognition by C3 Exoenzyme Based on C3-RhoA Complex Structure |
| 執筆形態 | その他 |
| 掲載誌名 | Journal of Biological Chemistry |
| 出版社・発行元 | American Society for Biochemistry {\&} Molecular Biology ({ASBMB}) |
| 巻・号・頁 | 290(32),pp.19423-19432 |
| 担当区分 | 最終著者,責任著者 |
| 著者・共著者 | Akiyuki Toda,Toshiharu Tsurumura,Toru Yoshida,Yayoi Tsumori,Hideaki Tsuge |
| 概要 | C3 exoenzyme is a mono-ADP-ribosyltransferase (ART) that catalyzes transfer of an ADP-ribose moiety from NAD(+) to Rho GTPases. C3 has long been used to study the diverse regulatory functions of Rho GTPases. How C3 recognizes its substrate and how ADP-ribosylation proceeds are still poorly understood. Crystal structures of C3-RhoA complex reveal that C3 recognizes RhoA via the switch I, switch II, and interswitch regions. In C3-RhoA(GTP) and C3-RhoA(GDP), switch I and II adopt the GDP and GTP conformations, respectively, which explains why C3 can ADP-ribosylate both nucleotide forms. Based on structural information, we successfully changed Cdc42 to an active substrate with combined mutations in the C3-Rho GTPase interface. Moreover, the structure reflects the close relationship among Gln-183 in the QXE motif (C3), a modified Asn-41 residue (RhoA) and NC1 of NAD(H), which suggests that C3 is the prototype ART. These structures show directly for the first time that the ARTT loop is the key to target protein recognition, and they also serve to bridge the gaps among independent studies of Rho GTPases and C3. |
| DOI | 10.1074/jbc.M115.653220 |
| ISSN | 0021-9258/1083-351X |
| Put Code(ORCID) | 42045690 |