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PDBsum entry 1qag

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protein Protein-protein interface(s) links
Structural protein PDB id
1qag
Jmol
Contents
Protein chain
226 a.a. *
Waters ×12
* Residue conservation analysis
PDB id:
1qag
Name: Structural protein
Title: Actin binding region of the dystrophin homologue utrophin
Structure: Utrophin actin binding region. Chain: a, b. Fragment: residues 28-261. Engineered: yes. Mutation: yes. Other_details: the biological assembly is probably the mono than the dimer. This may be in an open configuration as the are in the crystal or in a closed configuration with the re 148 and b153-b256 in the crystal being formed by a single c
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
3.00Å     R-factor:   0.198     R-free:   0.258
Authors: N.H.Keep,S.J.Winder,C.A.Moores,S.Walke,F.L.M.Norwood,J.Kendr
Key ref:
N.H.Keep et al. (1999). Crystal structure of the actin-binding region of utrophin reveals a head-to-tail dimer. Structure, 7, 1539-1546. PubMed id: 10647184 DOI: 10.1016/S0969-2126(00)88344-6
Date:
05-Mar-99     Release date:   01-Jan-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P46939  (UTRO_HUMAN) -  Utrophin
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
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Seq:
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Seq:
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Seq:
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Seq:
Struc:
3433 a.a.
226 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

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

 

 
DOI no: 10.1016/S0969-2126(00)88344-6 Structure 7:1539-1546 (1999)
PubMed id: 10647184  
 
 
Crystal structure of the actin-binding region of utrophin reveals a head-to-tail dimer.
N.H.Keep, S.J.Winder, C.A.Moores, S.Walke, F.L.Norwood, J.Kendrick-Jones.
 
  ABSTRACT  
 
BACKGROUND: Utrophin is a large multidomain protein that belongs to a superfamily of actin-binding proteins, which includes dystrophin, alpha-actinin, beta-spectrin, fimbrin, filamin and plectin. All the members of this family contain a common actin-binding region at their N termini and perform a wide variety of roles associated with the actin cytoskeleton. Utrophin is the autosomal homologue of dystrophin, the protein defective in the X-linked Duchenne and Becker muscular dystrophies, and upregulation of utrophin has been suggested as a potential therapy for muscular dystrophy patients. RESULTS: The structure of the actin-binding region of utrophin, consisting of two calponin-homology (CH) domains, has been solved at 3.0 A resolution. It is composed of an antiparallel dimer with each of the monomers being present in an extended dumbell shape and the two CH domains being separated by a long central helix. This extended conformation is in sharp contrast to the compact monomer structure of the N-terminal actin-binding region of fimbrin. CONCLUSIONS: The crystal structure of the actin-binding region of utrophin suggests that these actin-binding domains may be more flexible than was previously thought and that this flexibility may allow domain reorganisation and play a role in the actin-binding mechanism. Thus utrophin could possibly bind to actin in an extended conformation so that the sites previously identified as being important for actin binding may be directly involved in this interaction.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Similarity of CH domains of utrophin to other structures. (a) Stereo pair of superimposed a-carbon backbones for CH2 domains of utrophin (red), spectrin (blue) [17], fimbrin CH1.1 (purple) and fimbrin CH2.1 (green) [18], and utrophin CH1 (yellow). The utrophin sequence is numbered at every ten residues. The superpositions were calculated on helices a1, a3, a4 and a6 using LSQMAN [52]. (b) Stereo pair of the a-carbon backbone of the dimer structure shown in Figure 1a (rotated by 90° about the normal to the page); chain A is in red and chain B is in blue. Fimbrin (green) is superposed on the utrophin CH1 domain of A and CH2 domain of B. The red copy of the utrophin monomer is labelled every 20 residues. The figure was produced using BOBSCRIPT [51].
 
  The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 1539-1546) copyright 1999.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20446344 S.H.Lee, and R.Dominguez (2010).
Regulation of actin cytoskeleton dynamics in cells.
  Mol Cells, 29, 311-325.  
20383143 V.E.Galkin, A.Orlova, A.Salmazo, K.Djinovic-Carugo, and E.H.Egelman (2010).
Opening of tandem calponin homology domains regulates their affinity for F-actin.
  Nat Struct Mol Biol, 17, 614-616.
PDB code: 3lue
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.  
19169097 E.M.Strehle (2008).
Dysferlinopathy: from gene to protein.
  J Clin Neuromuscul Dis, 10, 83-84.  
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
17222516 C.Antolik, D.H.Catino, A.M.O'Neill, W.G.Resneck, J.A.Ursitti, and R.J.Bloch (2007).
The actin binding domain of ACF7 binds directly to the tetratricopeptide repeat domains of rapsyn.
  Neuroscience, 145, 56-65.  
16855024 C.Alewine, O.Olsen, J.B.Wade, and P.A.Welling (2006).
TIP-1 has PDZ scaffold antagonist activity.
  Mol Biol Cell, 17, 4200-4211.  
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
16109370 I.Hayashi, A.Wilde, T.K.Mal, and M.Ikura (2005).
Structural basis for the activation of microtubule assembly by the EB1 and p150Glued complex.
  Mol Cell, 19, 449-460.
PDB code: 1txq
15826935 I.N.Rybakova, and J.M.Ervasti (2005).
Identification of spectrin-like repeats required for high affinity utrophin-actin interaction.
  J Biol Chem, 280, 23018-23023.  
15960882 V.Delanote, J.Vandekerckhove, and J.Gettemans (2005).
Plastins: versatile modulators of actin organization in (patho)physiological cellular processes.
  Acta Pharmacol Sin, 26, 769-779.  
15272162 C.H.Wang, M.K.Balasubramanian, and T.Dokland (2004).
Structure, crystal packing and molecular dynamics of the calponin-homology domain of Schizosaccharomyces pombe Rng2.
  Acta Crystallogr D Biol Crystallogr, 60, 1396-1403.
PDB codes: 1p2x 1p5s
15274909 E.H.Egelman (2004).
More insights into structural plasticity of actin binding proteins.
  Structure, 12, 909-910.  
15128297 J.Sevcík, L.Urbániková, J.Kost'an, L.Janda, and G.Wiche (2004).
Actin-binding domain of mouse plectin. Crystal structure and binding to vimentin.
  Eur J Biochem, 271, 1873-1884.
PDB codes: 1sh5 1sh6
15274920 M.G.Klein, W.Shi, U.Ramagopal, Y.Tseng, D.Wirtz, D.R.Kovar, C.J.Staiger, and S.C.Almo (2004).
Structure of the actin crosslinking core of fimbrin.
  Structure, 12, 999.
PDB codes: 1pxy 1rt8
15548864 W.Lehman, R.Craig, J.Kendrick-Jones, and A.J.Sutherland-Smith (2004).
An open or closed case for the conformation of calponin homology domains on F-actin?
  J Muscle Res Cell Motil, 25, 351-358.  
12657793 F.Ekström, G.Stier, and U.H.Sauer (2003).
Crystallization of the actin-binding domain of human alpha-actinin: analysis of microcrystals of SeMet-labelled protein.
  Acta Crystallogr D Biol Crystallogr, 59, 724-726.  
14517317 S.H.Litjens, J.Koster, I.Kuikman, S.van Wilpe, J.M.de Pereda, and A.Sonnenberg (2003).
Specificity of binding of the plectin actin-binding domain to beta4 integrin.
  Mol Biol Cell, 14, 4039-4050.  
12517699 S.J.Winder (2003).
Structural insights into actin-binding, branching and bundling proteins.
  Curr Opin Cell Biol, 15, 14-22.  
12716899 T.S.Fraley, T.C.Tran, A.M.Corgan, C.A.Nash, J.Hao, D.R.Critchley, and J.A.Greenwood (2003).
Phosphoinositide binding inhibits alpha-actinin bundling activity.
  J Biol Chem, 278, 24039-24045.  
12006649 I.N.Rybakova, J.R.Patel, K.E.Davies, P.D.Yurchenco, and J.M.Ervasti (2002).
Utrophin binds laterally along actin filaments and can couple costameric actin with sarcolemma when overexpressed in dystrophin-deficient muscle.
  Mol Biol Cell, 13, 1512-1521.  
12136158 L.Urbániková, L.Janda, A.Popov, G.Wiche, and J.Sevcík (2002).
Purification, crystallization and preliminary X-ray analysis of the plectin actin-binding domain.
  Acta Crystallogr D Biol Crystallogr, 58, 1368-1370.  
12237450 M.Novatchkova, and F.Eisenhaber (2002).
A CH domain-containing N terminus in NuMA?
  Protein Sci, 11, 2281-2284.  
11259305 A.Orlova, I.N.Rybakova, E.Prochniewicz, D.D.Thomas, J.M.Ervasti, and E.H.Egelman (2001).
Binding of dystrophin's tandem calponin homology domain to F-actin is modulated by actin's structure.
  Biophys J, 80, 1926-1931.  
11381081 N.Volkmann, D.DeRosier, P.Matsudaira, and D.Hanein (2001).
An atomic model of actin filaments cross-linked by fimbrin and its implications for bundle assembly and function.
  J Cell Biol, 153, 947-956.  
11166570 S.J.Winder (2001).
The complexities of dystroglycan.
  Trends Biochem Sci, 26, 118-124.  
10891857 C.A.Moores, and J.Kendrick-Jones (2000).
Biochemical characterisation of the actin-binding properties of utrophin.
  Cell Motil Cytoskeleton, 46, 116-128.  
10801490 F.L.Norwood, A.J.Sutherland-Smith, N.H.Keep, and J.Kendrick-Jones (2000).
The structure of the N-terminal actin-binding domain of human dystrophin and how mutations in this domain may cause Duchenne or Becker muscular dystrophy.
  Structure, 8, 481-491.
PDB code: 1dxx
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.