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protein ligands metals Protein-protein interface(s) links
Structural protein/structural protein re PDB id
3daw
Jmol
Contents
Protein chains
372 a.a.
140 a.a. *
Ligands
ATP
Metals
_CA
Waters ×123
* Residue conservation analysis
PDB id:
3daw
Name: Structural protein/structural protein re
Title: Structure of the actin-depolymerizing factor homology domain in complex with actin
Structure: Actin, alpha skeletal muscle. Chain: a. Synonym: alpha-actin-1. Twinfilin-1. Chain: b. Fragment: c-terminal domain, adf-h 2, unp residues 167-322. Synonym: protein a6. Engineered: yes. Mutation: yes
Source: Oryctolagus cuniculus. European rabbit,japanese white rabbit, domestic rabbit,rabbits. Organism_taxid: 9986. Mus musculus. Mouse. Organism_taxid: 10090. Gene: twf1. Expressed in: escherichia coli.
Resolution:
2.55Å     R-factor:   0.212     R-free:   0.279
Authors: V.O.Paavilainen,E.Oksanen,A.Goldman,P.Lappalainen
Key ref: V.O.Paavilainen et al. (2008). Structure of the actin-depolymerizing factor homology domain in complex with actin. J Cell Biol, 182, 51-59. PubMed id: 18625842 DOI: 10.1083/jcb.200803100
Date:
30-May-08     Release date:   29-Jul-08    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P68135  (ACTS_RABIT) -  Actin, alpha skeletal muscle
Seq:
Struc: 		377 a.a.
372 a.a.
Protein chain
Pfam   ArchSchema ?
Q91YR1  (TWF1_MOUSE) -  Twinfilin-1
Seq:
Struc: 		350 a.a.
140 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   9 terms 
  Biological process     apoptosis   10 terms 
  Biochemical function     nucleotide binding     6 terms  

 

 
DOI no: 10.1083/jcb.200803100 J Cell Biol 182:51-59 (2008)
PubMed id: 18625842  
 
 
Structure of the actin-depolymerizing factor homology domain in complex with actin.
V.O.Paavilainen, E.Oksanen, A.Goldman, P.Lappalainen.
 
  ABSTRACT  
 
Actin dynamics provide the driving force for many cellular processes including motility and endocytosis. Among the central cytoskeletal regulators are actin-depolymerizing factor (ADF)/cofilin, which depolymerizes actin filaments, and twinfilin, which sequesters actin monomers and caps filament barbed ends. Both interact with actin through an ADF homology (ADF-H) domain, which is also found in several other actin-binding proteins. However, in the absence of an atomic structure for the ADF-H domain in complex with actin, the mechanism by which these proteins interact with actin has remained unknown. Here, we present the crystal structure of twinfilin's C-terminal ADF-H domain in complex with an actin monomer. This domain binds between actin subdomains 1 and 3 through an interface that is conserved among ADF-H domain proteins. Based on this structure, we suggest a mechanism by which ADF/cofilin and twinfilin inhibit nucleotide exchange of actin monomers and present a model for how ADF/cofilin induces filament depolymerization by weakening intrafilament interactions.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21314430 R.Dominguez, and K.C.Holmes (2011).
Actin structure and function.
  Annu Rev Biophys, 40, 169-186.  
20718862 A.V.Pivovarova, S.Y.Khaitlina, and D.I.Levitsky (2010).
Specific cleavage of the DNase-I binding loop dramatically decreases the thermal stability of actin.
  FEBS J, 277, 3812-3822.  
20347847 E.E.Grintsevich, V.E.Galkin, A.Orlova, A.J.Ytterberg, M.M.Mikati, D.S.Kudryashov, J.A.Loo, E.H.Egelman, and E.Reisler (2010).
Mapping of drebrin binding site on F-actin.
  J Mol Biol, 398, 542-554.  
20672362 G.Hild, B.Bugyi, and M.Nyitrai (2010).
Conformational dynamics of actin: effectors and implications for biological function.
  Cytoskeleton (Hoboken), 67, 609-629.  
20483342 H.Zhao, M.Hakala, and P.Lappalainen (2010).
ADF/cofilin binds phosphoinositides in a multivalent manner to act as a PIP(2)-density sensor.
  Biophys J, 98, 2327-2336.  
20368459 J.Pfaendtner, E.M.De La Cruz, and G.A.Voth (2010).
Actin filament remodeling by actin depolymerization factor/cofilin.
  Proc Natl Acad Sci U S A, 107, 7299-7304.  
20532239 M.Hertzog, F.Milanesi, L.Hazelwood, A.Disanza, H.Liu, E.Perlade, M.G.Malabarba, S.Pasqualato, A.Maiolica, S.Confalonieri, C.Le Clainche, N.Offenhauser, J.Block, K.Rottner, P.P.Di Fiore, M.F.Carlier, N.Volkmann, D.Hanein, and G.Scita (2010).
Molecular basis for the dual function of Eps8 on actin dynamics: bundling and capping.
  PLoS Biol, 8, e1000387.  
20446344 S.H.Lee, and R.Dominguez (2010).
Regulation of actin cytoskeleton dynamics in cells.
  Mol Cells, 29, 311-325.  
  20009568 S.I.Galkina, V.I.Stadnichuk, J.G.Molotkovsky, J.M.Romanova, G.F.Sud'ina, and T.Klein (2010).
Microbial alkaloid staurosporine induces formation of nanometer-wide membrane tubular extensions (cytonemes, membrane tethers) in human neutrophils.
  Cell Adh Migr, 4, 32-38.  
20637412 T.Oda, and Y.Maéda (2010).
Multiple Conformations of F-actin.
  Structure, 18, 761-767.  
19768801 A.K.Goroncy, S.Koshiba, N.Tochio, T.Tomizawa, M.Sato, M.Inoue, S.Watanabe, Y.Hayashizaki, A.Tanaka, T.Kigawa, and S.Yokoyama (2009).
NMR solution structures of actin depolymerizing factor homology domains.
  Protein Sci, 18, 2384-2392.
PDB codes: 1udm 1v6f 1wfs 1x67 2d8b
20700473 E.M.De La Cruz (2009).
How cofilin severs an actin filament.
  Biophys Rev, 1, 51-59.  
19289059 R.Kardos, K.Pozsonyi, E.Nevalainen, P.Lappalainen, M.Nyitrai, and G.Hild (2009).
The effects of ADF/cofilin and profilin on the conformation of the ATP-binding cleft of monomeric actin.
  Biophys J, 96, 2335-2343.  
19741095 S.Leyman, M.Sidani, L.Ritsma, D.Waterschoot, R.Eddy, D.Dewitte, O.Debeir, C.Decaestecker, J.Vandekerckhove, J.van Rheenen, C.Ampe, J.Condeelis, and M.Van Troys (2009).
Unbalancing the phosphatidylinositol-4,5-bisphosphate-cofilin interaction impairs cell steering.
  Mol Biol Cell, 20, 4509-4523.  
19935871 S.P.Yates, A.Loncar, and J.F.Dawson (2009).
Actin polymerization is controlled by residue size at position 204.
  Biochem Cell Biol, 87, 853-865.  
19720013 T.Shemesh, A.B.Verkhovsky, T.M.Svitkina, A.D.Bershadsky, and M.M.Kozlov (2009).
Role of focal adhesions and mechanical stresses in the formation and progression of the lamellipodium-lamellum interface [corrected].
  Biophys J, 97, 1254-1264.  
19008859 S.Mouilleron, S.Guettler, C.A.Langer, R.Treisman, and N.Q.McDonald (2008).
Molecular basis for G-actin binding to RPEL motifs from the serum response factor coactivator MAL.
  EMBO J, 27, 3198-3208.
PDB codes: 2v51 2v52
18982060 X.Fan, S.Martin-Brown, L.Florens, and R.Li (2008).
Intrinsic capability of budding yeast cofilin to promote turnover of tropomyosin-bound actin filaments.
  PLoS ONE, 3, e3641.  
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.