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PDBsum entry 1sgh
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protein links
Structural protein PDB id
1sgh
Contents
Protein chains
294 a.a. *
38 a.a.* *
* Residue conservation analysis
* C-alpha coords only
PDB id:
1sgh
Name: Structural protein
Title: Moesin ferm domain bound to ebp50 c-terminal peptide
Structure: Moesin. Chain: a. Fragment: ferm domain. Synonym: membrane-organizing extension spike protein. Engineered: yes. Ezrin-radixin-moesin binding phosphoprotein 50. Chain: b. Synonym: ebp50, na+, /h+, exchange regulatory cofactor nhe-rf, nherf- 1, regulatory cofactor of na+, /h+, exchanger, sodium-hydrogen
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: msn. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this sequence ocurrs naturally in humans
Biol. unit: Dimer (from PQS)
Resolution:
3.50Å     R-factor:   0.338     R-free:   0.401
Authors: C.M.Finnerty,D.Chambers,J.Ingraffea,H.R.Faber,P.A.Karplus,A.Bretscher
Key ref: C.M.Finnerty et al. (2004). The EBP50-moesin interaction involves a binding site regulated by direct masking on the FERM domain. J Cell Sci, 117, 1547-1552. PubMed id: 15020681
Date:
23-Feb-04     Release date:   29-Jun-04    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P26038  (MOES_HUMAN) -  Moesin from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		577 a.a.
294 a.a.
Protein chain
Pfam   ArchSchema ?
O14745  (NHRF1_HUMAN) -  Na(+)/H(+) exchange regulatory cofactor NHE-RF1 from Homo sapiens
Seq:
Struc: 		358 a.a.
38 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
    Key reference    
 
 
J Cell Sci 117:1547-1552 (2004)
PubMed id: 15020681  
 
 
The EBP50-moesin interaction involves a binding site regulated by direct masking on the FERM domain.
C.M.Finnerty, D.Chambers, J.Ingraffea, H.R.Faber, P.A.Karplus, A.Bretscher.
 
  ABSTRACT  
 
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 A 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 alpha-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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21444686 S.S.Francis, J.Sfakianos, B.Lo, and I.Mellman (2011).
A hierarchy of signals regulates entry of membrane proteins into the ciliary membrane domain in epithelial cells.
  J Cell Biol, 193, 219-233.  
20937695 D.Garbett, D.P.LaLonde, and A.Bretscher (2010).
The scaffolding protein EBP50 regulates microvillar assembly in a phosphorylation-dependent manner.
  J Cell Biol, 191, 397-413.  
20546116 K.H.Zawawi, A.Kantarci, U.Schulze-Späte, T.Fujita, E.L.Batista, S.Amar, and T.E.Van Dyke (2010).
Moesin-induced signaling in response to lipopolysaccharide in macrophages.
  J Periodontal Res, 45, 589-601.  
20308985 R.G.Fehon, A.I.McClatchey, and A.Bretscher (2010).
Organizing the cell cortex: the role of ERM proteins.
  Nat Rev Mol Cell Biol, 11, 276-287.  
19173579 D.P.LaLonde, and A.Bretscher (2009).
The scaffold protein PDZK1 undergoes a head-to-tail intramolecular association that negatively regulates its interaction with EBP50.
  Biochemistry, 48, 2261-2271.  
19556303 J.L.Espinoza, H.Takamatsu, X.Lu, Z.Qi, and S.Nakao (2009).
Anti-moesin antibodies derived from patients with aplastic anemia stimulate monocytic cells to secrete TNF-alpha through an ERK1/2-dependent pathway.
  Int Immunol, 21, 913-923.  
19596566 U.Tepass (2009).
FERM proteins in animal morphogenesis.
  Curr Opin Genet Dev, 19, 357-367.  
18086884 B.K.Cole, M.Curto, A.W.Chan, and A.I.McClatchey (2008).
Localization to the cortical cytoskeleton is necessary for Nf2/merlin-dependent epidermal growth factor receptor silencing.
  Mol Cell Biol, 28, 1274-1284.  
17242191 F.C.Morales, Y.Takahashi, S.Momin, H.Adams, X.Chen, and M.M.Georgescu (2007).
NHERF1/EBP50 head-to-tail intramolecular interaction masks association with PDZ domain ligands.
  Mol Cell Biol, 27, 2527-2537.  
17548515 M.Curto, B.K.Cole, D.Lallemand, C.H.Liu, and A.I.McClatchey (2007).
Contact-dependent inhibition of EGFR signaling by Nf2/Merlin.
  J Cell Biol, 177, 893-903.  
17134719 Q.Li, M.R.Nance, R.Kulikauskas, K.Nyberg, R.Fehon, P.A.Karplus, A.Bretscher, and J.J.Tesmer (2007).
Self-masking in an intact ERM-merlin protein: an active role for the central alpha-helical domain.
  J Mol Biol, 365, 1446-1459.
PDB codes: 2i1j 2i1k
17145964 A.Hanono, D.Garbett, D.Reczek, D.N.Chambers, and A.Bretscher (2006).
EPI64 regulates microvillar subdomains and structure.
  J Cell Biol, 175, 803-813.  
16540524 B.Cha, M.Tse, C.Yun, O.Kovbasnjuk, S.Mohan, A.Hubbard, M.Arpin, and M.Donowitz (2006).
The NHE3 juxtamembrane cytoplasmic domain directly binds ezrin: dual role in NHE3 trafficking and mobility in the brush border.
  Mol Biol Cell, 17, 2661-2673.  
17178913 H.Chiba, N.Sakai, M.Murata, M.Osanai, T.Ninomiya, T.Kojima, and N.Sawada (2006).
The nuclear receptor hepatocyte nuclear factor 4alpha acts as a morphogen to induce the formation of microvilli.
  J Cell Biol, 175, 971-980.  
15531580 H.Shiue, M.W.Musch, Y.Wang, E.B.Chang, and J.R.Turner (2005).
Akt2 phosphorylates ezrin to trigger NHE3 translocation and activation.
  J Biol Chem, 280, 1688-1695.  
15147559 A.Ivetic, and A.J.Ridley (2004).
Ezrin/radixin/moesin proteins and Rho GTPase signalling in leucocytes.
  Immunology, 112, 165-176.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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