![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article incl. Suppl. Information)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB |
| Item Type: | Article |
|---|---|
| Title: | The crystal structure of the RhoA-AKAP-Lbc DH-PH domain complex |
| Creators Name: | Abdul Azeez, K.R., Knapp, S., Fernandes, J.M.P., Klussmann, E. and Elkins, J.M. |
| Abstract: | The RhoGEF domain of AKAP-Lbc (AKAP13) catalyses nucleotide exchange on RhoA and is involved in development of cardiac hypertrophy. The RhoGEF activity of AKAP-Lbc has also been implicated in cancer. We have determined the X-ray crystal structure of the complex between RhoA:GDP and the AKAP-Lbc RhoGEF (DH-PH) domain to 2.1 {Angstrom} resolution. The structure reveals important differences compared to related RhoGEF proteins such as Leukemia-associated RhoGEF. Nucleotide exchange assays comparing the activity of the DH-PH domain to the DH domain alone showed no role for the PH domain in nucleotide exchange, which is explained by the RhoA:AKAP-Lbc structure. Comparison to a structure of the isolated AKAP-Lbc DH domain revealed a change in conformation of the N-terminal 'GEF switch' region upon binding to RhoA. Isothermal titration calorimetry showed that AKAP-Lbc has only micromolar affinity for RhoA which combined with the presence of potential binding pockets for small molecules on AKAP-Lbc raises the possibility of targeting AKAP-Lbc with guanine nucleotide exchange factor inhibitors. |
| Keywords: | AKAP13, AKAP-Lbc, GTPase, RhoGEF |
| Source: | Biochemical Journal |
| ISSN: | 0264-6021 |
| Publisher: | Portland Press |
| Volume: | 464 |
| Number: | 2 |
| Page Range: | 231-239 |
| Date: | 1 December 2014 |
| Additional Information: | Copyright © 2014 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC-BY) (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Official Publication: | https://doi.org/10.1042/BJ20140606 |
| External Fulltext: | View full text on PubMed Central |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
