spacer
spacer

PDBsum entry 2w0p

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Cell adhesion PDB id
2w0p
Jmol
Contents
Protein chains
93 a.a. *
Ligands
ARG-VAL-ALA-SER-
SER-VAL-PHE-ILE-
THR
SO4 ×2
Waters ×70
* Residue conservation analysis
PDB id:
2w0p
Name: Cell adhesion
Title: Crystal structure of the filamin a repeat 21 complexed with the migfilin peptide
Structure: Filamin-a. Chain: a, b. Fragment: ig-21, residues 2236-2329. Synonym: alpha-filamin, filamin-1, endothelial actin-binding protein, actin-binding protein 280, abp-280, nonmuscle filamin. Engineered: yes. Filamin-binding lim protein 1. Chain: c.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693. Synthetic: yes. Organism_taxid: 9606
Resolution:
1.90Å     R-factor:   0.210     R-free:   0.239
Authors: S.Ruskamo,J.Ylanne
Key ref:
Y.Lad et al. (2008). Structural Basis of the Migfilin-Filamin Interaction and Competition with Integrin {beta} Tails. J Biol Chem, 283, 35154-35163. PubMed id: 18829455 DOI: 10.1074/jbc.M802592200
Date:
20-Aug-08     Release date:   30-Sep-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P21333  (FLNA_HUMAN) -  Filamin-A
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
2647 a.a.
93 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     actin filament binding     1 term  

 

 
DOI no: 10.1074/jbc.M802592200 J Biol Chem 283:35154-35163 (2008)
PubMed id: 18829455  
 
 
Structural Basis of the Migfilin-Filamin Interaction and Competition with Integrin {beta} Tails.
Y.Lad, P.Jiang, S.Ruskamo, D.S.Harburger, J.Ylänne, I.D.Campbell, D.A.Calderwood.
 
  ABSTRACT  
 
A link between sites of cell adhesion and the cytoskeleton is essential for regulation of cell shape, motility, and signaling. Migfilin is a recently identified adaptor protein that localizes at cell-cell and cell-extracellular matrix adhesion sites, where it is thought to provide a link to the cytoskeleton by interacting with the actin cross-linking protein filamin. Here we have used x-ray crystallography, NMR spectroscopy, and protein-protein interaction studies to investigate the molecular basis of migfilin binding to filamin. We report that the N-terminal portion of migfilin can bind all three human filamins (FLNa, -b, or -c) and that there are multiple migfilin-binding sites in FLNa. Human filamins are composed of an N-terminal actin-binding domain followed by 24 immunoglobulin-like (IgFLN) domains and we find that migfilin binds preferentially to IgFLNa21 and more weakly to IgFLNa19 and -22. The filamin-binding site in migfilin is localized between Pro(5) and Pro(19) and binds to the CD face of the IgFLNa21 beta-sandwich. This interaction is similar to the previously characterized beta7 integrin-IgFLNa21 interaction and migfilin and integrin beta tails can compete with one another for binding to IgFLNa21. This suggests that competition between filamin ligands for common binding sites on IgFLN domains may provide a general means of modulating filamin interactions and signaling. In this specific case, displacement of integrin tails from filamin by migfilin may provide a mechanism for switching between different integrin-cytoskeleton linkages.
 
  Selected figure(s)  
 
Figure 4.
Structure of IgFLNa21/Pro^5-Pro^19 migfilin peptide complex. A, overall structure of the IgFLNa21 Pro^5-Pro^19 migfilin peptide complex shown as a schematic. N and C termini are indicated. Migfilin peptide (blue) is surrounded by two IgFLNa21 domains, chain A (yellow) and chain B (orange). B, electron density map (F[o] - F[c]) of the migfilin peptide without peptide calculated from the final model without the peptide and shown at σ level 3.0. C, the same panel as B but with migfilin peptide. D, details of residues participating in the interaction of IgFLNa21 chain A and migfilin peptide. Most side chains of peptide residues interact with residues of the IgFLNa21 D-strand. Residues likely to be important for the interaction are named. The backbone hydrogen bonds are shown with blue dashed lines and side chain hydrogen bonds with red. Ser^11 and Val^13 were modeled in 2 alternative conformations. E, details of the side chain interactions between IgFLNa21 chain B and migfilin peptide. F and G, superposition of the IgFLNa21-β7 integrin complex (PDB 2BRQ) with the IgFLNa21 chain A-migfilin (F), or IgFLNa21 chain B-migfilin (G) structures. IgFLNa21 strands C and D are shown as schematics with the integrin and migfilin peptides as stick models. Colors of the IgFLNa21-migfilin complex are as in panel A, the IgFLNa21-β7 complex is shown in pale blue.
Figure 7.
Migfilin-filamin interactions target migfilin to stress fibers. Immunofluorescence of GFP-migfilin or 1-85 mutant-transfected NIH3T3 cells attached to fibronectin-coated coverslips for 4 h prior to fixation. A, cells were stained for actin with phalloidin-Alexa 568; or B, endogenous FLNa.
 
  The above figures are reprinted from an Open Access publication published by the ASBMB: J Biol Chem (2008, 283, 35154-35163) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21311561 H.B.Schiller, C.C.Friedel, C.Boulegue, and R.Fässler (2011).
Quantitative proteomics of the integrin adhesome show a myosin II-dependent recruitment of LIM domain proteins.
  EMBO Rep, 12, 259-266.  
21597477 N.Hogg, I.Patzak, and F.Willenbrock (2011).
The insider's guide to leukocyte integrin signalling and function.
  Nat Rev Immunol, 11, 416-426.  
20061151 A.X.Zhou, J.H.Hartwig, and L.M.Akyürek (2010).
Filamins in cell signaling, transcription and organ development.
  Trends Cell Biol, 20, 113-123.  
19805437 B.A.Kesner, S.L.Milgram, B.R.Temple, and N.V.Dokholyan (2010).
Isoform divergence of the filamin family of proteins.
  Mol Biol Evol, 27, 283-295.  
20404115 D.C.Worth, K.Hodivala-Dilke, S.D.Robinson, S.J.King, P.E.Morton, F.B.Gertler, M.J.Humphries, and M.Parsons (2010).
Alpha v beta3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration.
  J Cell Biol, 189, 369-383.  
20048261 F.Ye, G.Hu, D.Taylor, B.Ratnikov, A.A.Bobkov, M.A.McLean, S.G.Sligar, K.A.Taylor, and M.H.Ginsberg (2010).
Recreation of the terminal events in physiological integrin activation.
  J Cell Biol, 188, 157-173.  
20308986 S.J.Shattil, C.Kim, and M.H.Ginsberg (2010).
The final steps of integrin activation: the end game.
  Nat Rev Mol Cell Biol, 11, 288-300.  
19804783 B.T.Goult, M.Bouaouina, D.S.Harburger, N.Bate, B.Patel, N.J.Anthis, I.D.Campbell, D.A.Calderwood, I.L.Barsukov, G.C.Roberts, and D.R.Critchley (2009).
The structure of the N-terminus of kindlin-1: a domain important for alphaiibbeta3 integrin activation.
  J Mol Biol, 394, 944-956.
PDB code: 2kmc
19289150 C.G.Gahmberg, S.C.Fagerholm, S.M.Nurmi, T.Chavakis, S.Marchesan, and M.Grönholm (2009).
Regulation of integrin activity and signalling.
  Biochim Biophys Acta, 1790, 431-444.  
19553810 E.F.Plow, J.Qin, and T.Byzova (2009).
Kindling the flame of integrin activation and function with kindlins.
  Curr Opin Hematol, 16, 323-328.  
19833732 J.Zhao, Y.Zhang, S.S.Ithychanda, Y.Tu, K.Chen, J.Qin, and C.Wu (2009).
Migfilin interacts with Src and contributes to cell-matrix adhesion-mediated survival signaling.
  J Biol Chem, 284, 34308-34320.  
19915675 M.Baldassarre, Z.Razinia, C.F.Burande, I.Lamsoul, P.G.Lutz, and D.A.Calderwood (2009).
Filamins regulate cell spreading and initiation of cell migration.
  PLoS One, 4, e7830.  
19622754 O.K.Heikkinen, S.Ruskamo, P.V.Konarev, D.I.Svergun, T.Iivanainen, S.M.Heikkinen, P.Permi, H.Koskela, I.Kilpeläinen, and J.Ylänne (2009).
Atomic structures of two novel immunoglobulin-like domain pairs in the actin cross-linking protein filamin.
  J Biol Chem, 284, 25450-25458.
PDB codes: 2k7p 2k7q
19630802 S.J.Shattil (2009).
The beta3 integrin cytoplasmic tail: protein scaffold and control freak.
  J Thromb Haemost, 7, 210-213.  
19828450 S.S.Ithychanda, D.Hsu, H.Li, L.Yan, D.D.Liu, D.Liu, M.Das, E.F.Plow, and J.Qin (2009).
Identification and characterization of multiple similar ligand-binding repeats in filamin: implication on filamin-mediated receptor clustering and cross-talk.
  J Biol Chem, 284, 35113-35121.  
19074766 S.S.Ithychanda, M.Das, Y.Q.Ma, K.Ding, X.Wang, S.Gupta, C.Wu, E.F.Plow, and J.Qin (2009).
Migfilin, a molecular switch in regulation of integrin activation.
  J Biol Chem, 284, 4713-4722.
PDB code: 2k9u
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 code is shown on the right.