In:
Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 12, No. 11_Supplement ( 2013-11-01), p. C298-C298
Abstract:
Merlin is a tumor suppressor protein that inhibits cell proliferation upon establishing cell-cell contacts. Because Merlin is homologous to the Ezrin-Radixin-Moesin (ERM) family of proteins, the structural model of ERM proteins cycling between closed/resting and open/active conformational states is employed to explain Merlin function. Nevertheless, using the ERM protein model has generated confusion about the mechanisms of Merlin tumor suppressor activity. Here, using contrast-matching small angle neutron scattering (SANS), we have determined the molecular shapes of Merlin and its phosphomimetic Merlin(S518D) mutant. In solution, both Merlin and Merlin(S518D) adopted a closed conformation that is capable of binding to the scaffolding protein NHERF1 with comparable binding affinities. However, in the presence of the phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), the wild-type Merlin shifts toward an open conformation whereas Merlin(S518D) remains locked in a closed conformation. Our data implied that although Merlin has similar molecular shape as ERM proteins, it has different protein-binding properties, and phosphorylation and PI(4,5)P2-binding modulate its conformational changes differently from ERM proteins. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C298. Citation Format: Jahan Ali Khajeh, Moussoubaou Atchiba, Zimei Bu. Conformational characterization of tumor suppressor protein Merlin and phosphomimetic Merlin(S518D) mutant in solution. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C298.
Type of Medium:
Online Resource
ISSN:
1535-7163
,
1538-8514
DOI:
10.1158/1535-7163.TARG-13-C298
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2062135-8
SSG:
12
