論文 - 詳細
| RRC ID | 35465 |
|---|---|
| 著者 | Gavriljuk K, Gazdag EM, Itzen A, Kötting C, Goody RS, Gerwert K. |
| タイトル | Catalytic mechanism of a mammalian Rab·RabGAP complex in atomic detail. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
Rab GTPases, key regulators of vesicular transport, hydrolyze GTP very slowly unless assisted by Rab GTPase-activating proteins (RabGAPs). Dysfunction of RabGAPs is involved in many diseases. By combining X-ray structure analysis and time-resolved FTIR spectroscopy we reveal here the detailed molecular reaction mechanism of a complex between human Rab and RabGAP at the highest possible spatiotemporal resolution and in atomic detail. A glutamine residue of Rab proteins (cis-glutamine) that is essential for intrinsic activity is less important in the GAP-activated reaction. During generation of the RabGAP·Rab:GTP complex, there is a rapid conformational change in which the cis-glutamine is replaced by a glutamine from RabGAP (trans-glutamine); this differs from the RasGAP mechanism, where the cis-glutamine is also important for GAP catalysis. However, as in the case of Ras, a trans-arginine is also recruited to complete the active center during this conformational change. In contrast to the RasGAP mechanism, an accumulation of a state in which phosphate is bound is not observed, and bond breakage is the rate-limiting step. The movement of trans-glutamine and trans-arginine into the catalytic site and bond breakage during hydrolysis are monitored in real time. The combination of X-ray structure analysis and time-resolved FTIR spectroscopy provides detailed insight in the catalysis of human Rab GTPases. |
| 巻・号 | 109(52) |
| ページ | 21348-53 |
| 公開日 | 2012-12-26 |
| DOI | 10.1073/pnas.1214431110 |
| PII | 1214431110 |
| PMID | 23236136 |
| PMC | PMC3535612 |
| MeSH | Animals Biocatalysis* Catalytic Domain DNA Mutational Analysis GTPase-Activating Proteins / chemistry GTPase-Activating Proteins / metabolism* Glutamine / metabolism Guanosine Triphosphate / metabolism Humans Hydrolysis Kinetics Mammals / metabolism* Models, Molecular* Spectroscopy, Fourier Transform Infrared rab1 GTP-Binding Proteins / chemistry rab1 GTP-Binding Proteins / metabolism* |
| IF | 9.412 |
| 引用数 | 38 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 原核生物(大腸菌) | ME8459(TH16#4)? |