QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online March 12, 2004
doi: 10.1242/10.1242/jcs.01038

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Finnerty, C. M. Articles by Bretscher, A. Search for Related Content PubMed PubMed Citation Articles by Finnerty, C. M. Articles by Bretscher, A. Social Bookmarking                         What's this?

The EBP50-moesin interaction involves a binding site regulated by direct masking on the FERM domain

¹ Department of Molecular Biology and Genetics, Biotechnology Building, Cornell University, Ithaca, NY14853, USA
² Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA

^* Author for correspondence (e-mail: apb5{at}cornell.edu)

Accepted 25 November 2003

Members of the ezrin-radixin-moesin (ERM) protein family serve as regulated microfilament-membrane crosslinking proteins that, upon activation, bind the scaffolding protein ERM-phosphoprotein of 50 kDa (EBP50). Here we report a 3.5 Å resolution diffraction analysis of a complex between the active moesin N-terminal FERM domain and a 38 residue peptide from the C terminus of EBP50. This crystallographic result, combined with sequence and structural comparisons, suggests that the C-terminal 11 residues of EBP50 binds as an -helix at the same site occupied in the dormant monomer by the last 11 residues of the inhibitory moesin C-terminal tail. Biochemical support for this interpretation derives from in vitro studies showing that appropriate mutations in both the EBP50 tail peptide and the FERM domain reduce binding, and that a peptide representing just the C-terminal 14 residues of EBP50 also binds to moesin. Combined with the recent identification of the I-CAM-2 binding site on the ERM FERM domain (Hamada, K., Shimizu, T., Yonemura, S., Tsukita, S., and Hakoshima, T. (2003) EMBO J. 22, 502-514), this study reveals that the FERM domain contains two distinct binding sites for membrane-associated proteins. The contribution of each ligand to ERM function can now be dissected by making structure-based mutations that specifically affect the binding of each ligand.

Key words: Moesin, Ezrin, EBP50, FERM

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. J. Mahon The Parathyroid Hormone 1 Receptor Directly Binds to the FERM Domain of Ezrin, an Interaction that Supports Apical Receptor Localization and Signaling in LLC-PK1 Cells Mol. Endocrinol., October 1, 2009; 23(10): 1691 - 1701. [Abstract] [Full Text] [PDF]

				J. L. Espinoza, H. Takamatsu, X. Lu, Z. Qi, and S. Nakao Anti-moesin antibodies derived from patients with aplastic anemia stimulate monocytic cells to secrete TNF-{alpha} through an ERK1/2-dependent pathway Int. Immunol., August 1, 2009; 21(8): 913 - 923. [Abstract] [Full Text] [PDF]

				B. K. Cole, M. Curto, A. W. Chan, and A. I. McClatchey Localization to the Cortical Cytoskeleton Is Necessary for Nf2/Merlin-Dependent Epidermal Growth Factor Receptor Silencing Mol. Cell. Biol., February 15, 2008; 28(4): 1274 - 1284. [Abstract] [Full Text] [PDF]

				M. Curto, B. K. Cole, D. Lallemand, C.-H. Liu, and A. I. McClatchey Contact-dependent inhibition of EGFR signaling by Nf2/Merlin J. Cell Biol., June 21, 2007; 177(5): 893 - 903. [Abstract] [Full Text] [PDF]

				F. C. Morales, Y. Takahashi, S. Momin, H. Adams, X. Chen, and M.-M. Georgescu NHERF1/EBP50 Head-to-Tail Intramolecular Interaction Masks Association with PDZ Domain Ligands Mol. Cell. Biol., April 1, 2007; 27(7): 2527 - 2537. [Abstract] [Full Text] [PDF]

				H. Chiba, N. Sakai, M. Murata, M. Osanai, T. Ninomiya, T. Kojima, and N. Sawada The nuclear receptor hepatocyte nuclear factor 4{alpha} acts as a morphogen to induce the formation of microvilli J. Cell Biol., December 18, 2006; 175(6): 971 - 980. [Abstract] [Full Text] [PDF]

				A. Hanono, D. Garbett, D. Reczek, D. N. Chambers, and A. Bretscher EPI64 regulates microvillar subdomains and structure J. Cell Biol., December 4, 2006; 175(5): 803 - 813. [Abstract] [Full Text] [PDF]

				B. Cha, M. Tse, C. Yun, O. Kovbasnjuk, S. Mohan, A. Hubbard, M. Arpin, and M. Donowitz The NHE3 Juxtamembrane Cytoplasmic Domain Directly Binds Ezrin: Dual Role in NHE3 Trafficking and Mobility in the Brush Border Mol. Biol. Cell, June 1, 2006; 17(6): 2661 - 2673. [Abstract] [Full Text] [PDF]

				J. Li, Z. Dai, D. Jana, D. J. E. Callaway, and Z. Bu Ezrin Controls the Macromolecular Complexes Formed between an Adapter Protein Na+/H+ Exchanger Regulatory Factor and the Cystic Fibrosis Transmembrane Conductance Regulator J. Biol. Chem., November 11, 2005; 280(45): 37634 - 37643. [Abstract] [Full Text] [PDF]

				T. Balla Inositol-lipid binding motifs: signal integrators through protein-lipid and protein-protein interactions J. Cell Sci., May 15, 2005; 118(10): 2093 - 2104. [Abstract] [Full Text] [PDF]

				H. Shiue, M. W. Musch, Y. Wang, E. B. Chang, and J. R. Turner Akt2 Phosphorylates Ezrin to Trigger NHE3 Translocation and Activation J. Biol. Chem., January 14, 2005; 280(2): 1688 - 1695. [Abstract] [Full Text] [PDF]