PDBsum entry 1h8b

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protein Protein-protein interface(s) links
Structural protein PDB id
Protein chains
73 a.a. *
23 a.a. *
* Residue conservation analysis
PDB id:
Name: Structural protein
Title: Ef-hands 3,4 from alpha-actinin / z-repeat 7 from titin
Structure: Alpha-actinin 2, skeletal muscle isoform. Chain: a. Fragment: ef-hands 3&4 residue 822-894. Synonym: act-ef34. Engineered: yes. Titin. Chain: b. Fragment: z-repeat 7 residues 648-698. Synonym: zr7.
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: muscle. Expressed in: escherichia coli. Expression_system_taxid: 562. Oryctolagus cuniculus. Rabbit. Organism_taxid: 9986.
NMR struc: 30 models
Authors: R.A.Atkinson,C.Joseph,G.Kelly,F.W.Muskett,T.A.Frenkiel, D.Nietlispach,A.Pastore
Key ref:
R.A.Atkinson et al. (2001). Ca2+-independent binding of an EF-hand domain to a novel motif in the alpha-actinin-titin complex. Nat Struct Biol, 8, 853-857. PubMed id: 11573089 DOI: 10.1038/nsb1001-853
01-Feb-01     Release date:   30-Aug-01    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P35609  (ACTN2_HUMAN) -  Alpha-actinin-2
894 a.a.
73 a.a.*
Protein chain
Pfam   ArchSchema ?
O97791  (O97791_RABIT) -  Titin (Fragment)
2000 a.a.
23 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     calcium ion binding     1 term  


DOI no: 10.1038/nsb1001-853 Nat Struct Biol 8:853-857 (2001)
PubMed id: 11573089  
Ca2+-independent binding of an EF-hand domain to a novel motif in the alpha-actinin-titin complex.
R.A.Atkinson, C.Joseph, G.Kelly, F.W.Muskett, T.A.Frenkiel, D.Nietlispach, A.Pastore.
The interaction between alpha-actinin and titin, two modular muscle proteins, is essential for sarcomere assembly. We have solved the solution structure of a complex between the calcium-insensitive C-terminal EF-hand domain of alpha-actinin-2 and the seventh Z-repeat of titin. The structure of the complex is in a semi-open conformation and closely resembles that of myosin light chains in their complexes with heavy chain IQ motifs. However, no IQ motif is present in the Z-repeat, suggesting that the semi-open conformation is a general structural solution for calcium-independent recognition of EF-hand domains.
  Selected figure(s)  
Figure 1.
Figure 1. Structure of the complex of -actinin-2 Act-EF34 with titin Zr7. a, Ribbon diagram of a representative structure. Act-EF34 is shown in gold and Zr7 in green. b, Stereo view of the bundle of 30 structures. The backbone atoms of Act-EF34 and Zr7 are shown in black and blue, respectively. Side chains involved in intermolecular contacts are shown in red (Act-EF34) and green (Zr7). The backbone atoms of Act-EF34 Glu 829 - Pro 867, Pro 876 -Leu 888 and Zr7 Ala 657 -Arg 671 were superimposed. The first and fourth helices run antiparallel (with interhelical angles of 149°), bringing the N- and C-termini close together. The second and third helices also run approximately antiparallel to one another (with interhelical angles of 142°) and form a second plane at 81° to the first. These values are close to the interhelix angles observed for the myosin light chain domains (the angles between helices 1 -4 and 2 -3 are 151° and 149° in RLC, and 147° and 131° in ELC, respectively. c, Stereo view showing the backbone (black) of a representative structure with the side chains of Act-EF34 (red) and Zr7 (green) that are involved in intermolecular contacts. The orientation is close to that in (b), rotated slightly for clarity.
Figure 4.
Figure 4. Comparison of the structure of the complex of -actinin-2 Act-EF34 -titin Zr7 with those of other representative EF-hand domain complexes. The structures shown, from top left to bottom right are: -actinin-2 Act-EF34 -titin Zr7 (gold and green; PDB code 1H8B); scallop myosin essential light chain -heavy chain (magenta and blue; 1WDC); scallop myosin regulatory light chain -heavy chain (cyan and black; 1WDC); partially Ca^2+-loaded calmodulin -potassium channel gating domain (gray and red; 1G4Y); troponin C -troponin I1 -47 (red and gray; 1A2X); Ca^2+-calmodulin -smooth muscle MLCK (green and orange; 1CDL); Ca^2+-calmodulin -C20W (blue and light pink; 1CFF); and Ca^2+ calmodulin -Ca^2+-calmodulin-dependent protein kinase (light purple and green; 1CKK). The N-terminus of the target peptides is indicated to stress the different chain directionality.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2001, 8, 853-857) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21190822 M.Gautel (2011).
The sarcomeric cytoskeleton: who picks up the strain?
  Curr Opin Cell Biol, 23, 39-46.  
  21465563 X.Xu, R.Ishima, and J.B.Ames (2011).
Conformational dynamics of recoverin's Ca(2+) -myristoyl switch probed by (15) N NMR relaxation dispersion and chemical shift analysis.
  Proteins, 79, 1910-1922.  
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.  
20056793 R.F.Robledo, A.J.Lambert, C.S.Birkenmeier, M.V.Cirlan, A.F.Cirlan, D.R.Campagna, S.E.Lux, and L.L.Peters (2010).
Analysis of novel sph (spherocytosis) alleles in mice reveals allele-specific loss of band 3 and adducin in {alpha}-spectrin-deficient red cells.
  Blood, 115, 1804-1814.  
  19789381 A.Kontrogianni-Konstantopoulos, M.A.Ackermann, A.L.Bowman, S.V.Yap, and R.J.Bloch (2009).
Muscle giants: molecular scaffolds in sarcomerogenesis.
  Physiol Rev, 89, 1217-1267.  
19815520 L.Lu, V.Timofeyev, N.Li, S.Rafizadeh, A.Singapuri, T.R.Harris, and N.Chiamvimonvat (2009).
Alpha-actinin2 cytoskeletal protein is required for the functional membrane localization of a Ca2+-activated K+ channel (SK2 channel).
  Proc Natl Acad Sci U S A, 106, 18402-18407.  
18996015 N.Pinotsis, P.Abrusci, K.Djinović-Carugo, and M.Wilmanns (2009).
Terminal assembly of sarcomeric filaments by intermolecular beta-sheet formation.
  Trends Biochem Sci, 34, 33-39.  
17894348 I.Hudáky, and A.Perczel (2008).
Prolylproline unit in model peptides and in fragments from databases.
  Proteins, 70, 1389-1407.  
18519573 R.J.Chi, A.R.Simon, E.A.Bienkiewicz, A.Felix, and T.C.Keller (2008).
Smooth muscle titin Zq domain interaction with the smooth muscle alpha-actinin central rod.
  J Biol Chem, 283, 20959-20967.  
17151196 A.Houdusse, J.F.Gaucher, E.Krementsova, S.Mui, K.M.Trybus, and C.Cohen (2006).
Crystal structure of apo-calmodulin bound to the first two IQ motifs of myosin V reveals essential recognition features.
  Proc Natl Acad Sci U S A, 103, 19326-19331.
PDB code: 2ix7
16877506 G.Fiorin, A.Pastore, P.Carloni, and M.Parrinello (2006).
Using metadynamics to understand the mechanism of calmodulin/target recognition at atomic detail.
  Biophys J, 91, 2768-2777.  
17170575 J.I.Alafag, E.K.Moon, Y.C.Hong, D.I.Chung, and H.H.Kong (2006).
Molecular and biochemical characterization of a novel actin bundling protein in Acanthamoeba.
  Korean J Parasitol, 44, 331-341.  
16407954 P.Zou, N.Pinotsis, S.Lange, Y.H.Song, A.Popov, I.Mavridis, O.M.Mayans, M.Gautel, and M.Wilmanns (2006).
Palindromic assembly of the giant muscle protein titin in the sarcomeric Z-disk.
  Nature, 439, 229-233.
PDB code: 1ya5
16341830 M.Marino, D.I.Svergun, L.Kreplak, P.V.Konarev, B.Maco, D.Labeit, and O.Mayans (2005).
Poly-Ig tandems from I-band titin share extended domain arrangements irrespective of the distinct features of their modular constituents.
  J Muscle Res Cell Motil, 26, 355-365.  
15833278 R.J.Chi, S.G.Olenych, K.Kim, and T.C.Keller (2005).
Smooth muscle alpha-actinin interaction with smitin.
  Int J Biochem Cell Biol, 37, 1470-1482.  
14982937 B.Bánfi, F.Tirone, I.Durussel, J.Knisz, P.Moskwa, G.Z.Molnár, K.H.Krause, and J.A.Cox (2004).
Mechanism of Ca2+ activation of the NADPH oxidase 5 (NOX5).
  J Biol Chem, 279, 18583-18591.  
15084604 T.Klaavuniemi, A.Kelloniemi, and J.Ylänne (2004).
The ZASP-like motif in actinin-associated LIM protein is required for interaction with the alpha-actinin rod and for targeting to the muscle Z-line.
  J Biol Chem, 279, 26402-26410.  
12517699 S.J.Winder (2003).
Structural insights into actin-binding, branching and bundling proteins.
  Curr Opin Cell Biol, 15, 14-22.  
12032157 E.Yus-Najera, I.Santana-Castro, and A.Villarroel (2002).
The identification and characterization of a noncontinuous calmodulin-binding site in noninactivating voltage-dependent KCNQ potassium channels.
  J Biol Chem, 277, 28545-28553.  
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.