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Structural protein PDB id
1mb8
Jmol
Contents
Protein chain
243 a.a. *
Waters ×153
* Residue conservation analysis
PDB id:
1mb8
Name: Structural protein
Title: Crystal structure of the actin binding domain of plectin
Structure: Plectin. Chain: a. Fragment: residues 59-293. Synonym: hd1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.15Å     R-factor:   0.212     R-free:   0.261
Authors: J.M.De Pereda
Key ref:
B.García-Alvarez et al. (2003). Structural and functional analysis of the actin binding domain of plectin suggests alternative mechanisms for binding to F-actin and integrin beta4. Structure, 11, 615-625. PubMed id: 12791251 DOI: 10.1016/S0969-2126(03)00090-X
Date:
02-Aug-02     Release date:   10-Jun-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q15149  (PLEC_HUMAN) -  Plectin
Seq:
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Seq:
Struc: 		4684 a.a.
243 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 14 residue positions (black crosses)

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

 

 
DOI no: 10.1016/S0969-2126(03)00090-X Structure 11:615-625 (2003)
PubMed id: 12791251  
 
 
Structural and functional analysis of the actin binding domain of plectin suggests alternative mechanisms for binding to F-actin and integrin beta4.
B.García-Alvarez, A.Bobkov, A.Sonnenberg, J.M.de Pereda.
 
  ABSTRACT  
 
Plectin is a widely expressed cytoskeletal linker. Here we report the crystal structure of the actin binding domain of plectin and show that this region is sufficient for interaction with F-actin or the cytoplasmic region of integrin alpha6beta4. The structure is formed by two calponin homology domains arranged in a closed conformation. We show that binding to F-actin induces a conformational change in plectin that is inhibited by an engineered interdomain disulfide bridge. A two-step induced fit mechanism involving binding and subsequent domain rearrangement is proposed. In contrast, interaction with integrin alpha6beta4 occurs in a closed conformation. Competitive binding of plectin to F-actin and integrin alpha6beta4 may rely on the observed alternative binding mechanisms and involve both allosteric and steric factors.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. Molecular Surface of Plectin ABDTwo views of the solvent-accessible surface colored according to electrostatic potential: blue for positive (20 kT/e), red for negative ( -20 kT/e). In the upper panel the ABD is in the same orientation as in Figure 1B. A basic cleft extends along the interdomain contact, and it is flanked by acidic residues.
 
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 615-625) copyright 2003.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20426868 J.M.Doolittle, and S.M.Gomez (2010).
Structural similarity-based predictions of protein interactions between HIV-1 and Homo sapiens.
  Virol J, 7, 82.  
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
19089942 A.Shvetsov, E.Berkane, D.Chereau, R.Dominguez, and E.Reisler (2009).
The actin-binding domain of cortactin is dynamic and unstructured and affects lateral and longitudinal contacts in F-actin.
  Cell Motil Cytoskeleton, 66, 90-98.  
19652713 B.Nabet, A.Tsai, J.W.Tobias, and R.P.Carstens (2009).
Identification of a putative network of actin-associated cytoskeletal proteins in glomerular podocytes defined by co-purified mRNAs.
  PLoS One, 4, e6491.  
19419971 J.Kostan, M.Gregor, G.Walko, and G.Wiche (2009).
Plectin Isoform-dependent Regulation of Keratin-Integrin {alpha}6{beta}4 Anchorage via Ca2+/Calmodulin.
  J Biol Chem, 284, 18525-18536.  
  19736524 J.M.de Pereda, E.Ortega, N.Alonso-García, M.Gómez-Hernández, and A.Sonnenberg (2009).
Advances and perspectives of the architecture of hemidesmosomes: lessons from structural biology.
  Cell Adh Migr, 3, 361-364.  
19242489 J.M.de Pereda, M.P.Lillo, and A.Sonnenberg (2009).
Structural basis of the interaction between integrin alpha6beta4 and plectin at the hemidesmosomes.
  EMBO J, 28, 1180-1190.
PDB codes: 3f7p 3f7q 3f7r
  19498002 R.Xu, S.DeVries, M.Camboni, and P.T.Martin (2009).
Overexpression of Galgt2 reduces dystrophic pathology in the skeletal muscles of alpha sarcoglycan-deficient mice.
  Am J Pathol, 175, 235-247.  
19923718 S.Ruskamo, and J.Ylänne (2009).
Structure of the human filamin A actin-binding domain.
  Acta Crystallogr D Biol Crystallogr, 65, 1217-1221.  
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.  
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
16757171 S.H.Litjens, J.M.de Pereda, and A.Sonnenberg (2006).
Current insights into the formation and breakdown of hemidesmosomes.
  Trends Cell Biol, 16, 376-383.  
15654952 A.E.Kalinin, A.E.Kalinin, M.Aho, J.Uitto, and S.Aho (2005).
Breaking the connection: caspase 6 disconnects intermediate filament-binding domain of periplakin from its actin-binding N-terminal region.
  J Invest Dermatol, 124, 46-55.  
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.  
15817481 S.H.Litjens, K.Wilhelmsen, J.M.de Pereda, A.Perrakis, and A.Sonnenberg (2005).
Modeling and experimental validation of the binary complex of the plectin actin-binding domain and the first pair of fibronectin type III (FNIII) domains of the beta4 integrin.
  J Biol Chem, 280, 22270-22277.  
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.  
15226304 G.J.Zwartz, A.Chigaev, D.C.Dwyer, T.D.Foutz, B.S.Edwards, and L.A.Sklar (2004).
Real-time analysis of very late antigen-4 affinity modulation by shear.
  J Biol Chem, 279, 38277-38286.  
15232572 J.J.Jefferson, C.L.Leung, and R.K.Liem (2004).
Plakins: goliaths that link cell junctions and the cytoskeleton.
  Nat Rev Mol Cell Biol, 5, 542-553.  
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.  
14501122 C.H.Wang, M.Walsh, M.K.Balasubramanian, and T.Dokland (2003).
Expression, purification, crystallization and preliminary crystallographic analysis of the calponin-homology domain of Rng2.
  Acta Crystallogr D Biol Crystallogr, 59, 1809-1812.  
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.  
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.