PDBsum entry 1wku

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protein Protein-protein interface(s) links
Contractile protein PDB id
Protein chains
225 a.a. *
Waters ×459
* Residue conservation analysis
PDB id:
Name: Contractile protein
Title: High resolution structure of the human alpha-actinin isoform 3
Structure: Alpha-actinin 3. Chain: a, b. Fragment: actin binding domain (abd). Synonym: alpha actinin skeletal muscle isoform 3, f-actin cross linking protein. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: actn3. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.60Å     R-factor:   0.182     R-free:   0.208
Authors: G.Franzot,B.Sjoblom,M.Gautel,K.Djinovic Carugo
Key ref:
G.Franzot et al. (2005). The crystal structure of the actin binding domain from alpha-actinin in its closed conformation: structural insight into phospholipid regulation of alpha-actinin. J Mol Biol, 348, 151-165. PubMed id: 15808860 DOI: 10.1016/j.jmb.2005.01.002
08-Jun-04     Release date:   17-May-05    
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Protein chains
Pfam   ArchSchema ?
Q08043  (ACTN3_HUMAN) -  Alpha-actinin-3
901 a.a.
225 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

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


DOI no: 10.1016/j.jmb.2005.01.002 J Mol Biol 348:151-165 (2005)
PubMed id: 15808860  
The crystal structure of the actin binding domain from alpha-actinin in its closed conformation: structural insight into phospholipid regulation of alpha-actinin.
G.Franzot, B.Sjöblom, M.Gautel, K.Djinović Carugo.
Alpha-actinin is the major F-actin crosslinking protein in both muscle and non-muscle cells. We report the crystal structure of the actin binding domain of human muscle alpha-actinin-3, which is formed by two consecutive calponin homology domains arranged in a "closed" conformation. Structural studies and available biochemical data on actin binding domains suggest that two calponin homology domains come in a closed conformation in the native apo-form, and that conformational changes involving the relative orientation of the two calponin homology domains are required for efficient binding to actin filaments. The actin binding activity of muscle isoforms is supposed to be regulated by phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), which binds to the second calponin homology domain. On the basis of structural analysis we propose a distinct binding site for PtdIns(4,5)P2, where the fatty acid moiety would be oriented in a direction that allows it to interact with the linker sequence between the actin binding domain and the first spectrin-like repeat, regulating thereby the binding of the C-terminal calmodulin-like domain to this linker.
  Selected figure(s)  
Figure 2.
Figure 2. (a) Structural superposition of ABDs from a-actinin and plectin made by TOPP. The color code for ABD from a-actinin is as in Figure 1, plectin is shown in blue. The superimposed proteins are oriented according to Figure 1. The Figure was prepared by PyMOL. (b) Structural superposition of ABDs from a-actinin and utrophin was made by TOPP. The color code for ABD from a-actinin is as in Figure 1, utrophin subunits are shown in yellow and in blue. The superimposed proteins are oriented according to Figure 1. The Figure was prepared by PyMOL.
Figure 3.
Figure 3. Dendrogram showing the classification of CH domains on the basis of their 3D structure.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 348, 151-165) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21241830 K.G.Oikonomou, K.Zachou, and G.N.Dalekos (2011).
Alpha-actinin: a multidisciplinary protein with important role in B-cell driven autoimmunity.
  Autoimmun Rev, 10, 389-396.  
21190822 M.Gautel (2011).
The sarcomeric cytoskeleton: who picks up the strain?
  Curr Opin Cell Biol, 23, 39-46.  
20585040 C.Korsgren, and S.E.Lux (2010).
The carboxyterminal EF domain of erythroid alpha-spectrin is necessary for optimal spectrin-actin binding.
  Blood, 116, 2600-2607.  
20446344 S.H.Lee, and R.Dominguez (2010).
Regulation of actin cytoskeleton dynamics in cells.
  Mol Cells, 29, 311-325.  
20696926 S.M.Singh, N.Kongari, J.Cabello-Villegas, and K.M.Mallela (2010).
Missense mutations in dystrophin that trigger muscular dystrophy decrease protein stability and lead to cross-beta aggregates.
  Proc Natl Acad Sci U S A, 107, 15069-15074.  
19773341 A.R.Clark, G.M.Sawyer, S.P.Robertson, and A.J.Sutherland-Smith (2009).
Skeletal dysplasias due to filamin A mutations result from a gain-of-function mechanism distinct from allelic neurological disorders.
  Hum Mol Genet, 18, 4791-4800.
PDB codes: 3hoc 3hop 3hor
19830582 P.K.Luther (2009).
The vertebrate muscle Z-disc: sarcomere anchor for structure and signalling.
  J Muscle Res Cell Motil, 30, 171-185.  
18952167 B.Sjöblom, J.Ylänne, and K.Djinović-Carugo (2008).
Novel structural insights into F-actin-binding and novel functions of calponin homology domains.
  Curr Opin Struct Biol, 18, 702-708.  
18296101 M.Lorenzi, and M.Gimona (2008).
Synthetic actin-binding domains reveal compositional constraints for function.
  Int J Biochem Cell Biol, 40, 1806-1816.  
18164029 S.H.Lee, A.Weins, D.B.Hayes, M.R.Pollak, and R.Dominguez (2008).
Crystal structure of the actin-binding domain of alpha-actinin-4 Lys255Glu mutant implicated in focal segmental glomerulosclerosis.
  J Mol Biol, 376, 317-324.
PDB code: 2r0o
17901210 A.Weins, J.S.Schlondorff, F.Nakamura, B.M.Denker, J.H.Hartwig, T.P.Stossel, and M.R.Pollak (2007).
Disease-associated mutant alpha-actinin-4 reveals a mechanism for regulating its F-actin-binding affinity.
  Proc Natl Acad Sci U S A, 104, 16080-16085.  
17331538 C.M.Hampton, D.W.Taylor, and K.A.Taylor (2007).
Novel structures for alpha-actinin:F-actin interactions and their implications for actin-membrane attachment and tension sensing in the cytoskeleton.
  J Mol Biol, 368, 92.  
17965186 S.J.Full, M.L.Deinzer, P.S.Ho, and J.A.Greenwood (2007).
Phosphoinositide binding regulates alpha-actinin CH2 domain structure: analysis by hydrogen/deuterium exchange mass spectrometry.
  Protein Sci, 16, 2597-2604.  
16781869 G.M.Popowicz, M.Schleicher, A.A.Noegel, and T.A.Holak (2006).
Filamins: promiscuous organizers of the cytoskeleton.
  Trends Biochem Sci, 31, 411-419.  
17043746 H.Sun, H.Dai, J.Zhang, X.Jin, S.Xiong, J.Xu, J.Wu, and Y.Shi (2006).
Solution structure of calponin homology domain of Human MICAL-1.
  J Biomol NMR, 36, 295-300.
PDB code: 2dk9
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.