PDBsum entry 1quu

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Contractile protein PDB id
Protein chain
248 a.a. *
Waters ×151
* Residue conservation analysis
PDB id:
Name: Contractile protein
Title: Crystal structure of two central spectrin-like repeats from alpha-actinin
Structure: Human skeletal muscle alpha-actinin 2. Chain: a. Fragment: spectrin-like repeats 2 and 3 - amino acids 391 to 637. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: skeletal muscle. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
2.50Å     R-factor:   0.229     R-free:   0.310
Authors: K.Djinovic-Carugo,P.Young,M.Gautel,M.Saraste
Key ref:
K.Djinović-Carugo et al. (1999). Structure of the alpha-actinin rod: molecular basis for cross-linking of actin filaments. Cell, 98, 537-546. PubMed id: 10481917 DOI: 10.1016/S0092-8674(00)81981-9
03-Jul-99     Release date:   20-Aug-99    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P35609  (ACTN2_HUMAN) -  Alpha-actinin-2
894 a.a.
248 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)


DOI no: 10.1016/S0092-8674(00)81981-9 Cell 98:537-546 (1999)
PubMed id: 10481917  
Structure of the alpha-actinin rod: molecular basis for cross-linking of actin filaments.
K.Djinović-Carugo, P.Young, M.Gautel, M.Saraste.
We have determined the crystal structure of the two central repeats in the alpha-actinin rod at 2.5 A resolution. The repeats are connected by a helical linker and form a symmetric, antiparallel dimer in which the repeats are aligned rather than staggered. Using this structure, which reveals the structural principle that governs the architecture of alpha-actinin, we have devised a plausible model of the entire alpha-actinin rod. The electrostatic properties explain how the two alpha-actinin subunits assemble in an antiparallel fashion, placing the actin-binding sites at both ends of the rod. This molecular architecture results in a protein that is able to form cross-links between actin filaments.
  Selected figure(s)  
Figure 3.
Figure 3. The Connecting LinkerClose-up of interactions between R2, R3, and the linker. The protein backbone is shown as a ribbon, and amino acid residues are drawn in a ball-and-stick representation. R2 is colored blue, R3 is green, and the linker is red.
Figure 6.
Figure 6. Model of the α-Actinin Rod(A) Sequence alignment of the α-actinin repeats used in modeling of repeats R1 and R4. Residue numbers for the full-length molecule and those of the construct used for the crystal structure are indicated at the edges and above the alignment, respectively. The α helices seen in the crystal structure are depicted as bars (blue for R2 and green for R3). The C termini of R1 and R3 and the N termini of R2 and R4, respectively, overlap due to the modeling procedure of R1 and R4. The overlapping residues shown in italic were used to assemble the model of the rod. The figure was generated with ALSCRIPT ([1]).(B) Ribbon diagram of α-actinin rod viewed in two orientations related by a 65 degree rotation around the long molecular axis through the central 2-fold axis. R1 is colored violet, R2 is blue, R3 is green, and R4 is yellow.(C) Electrostatic surface potential of one R1–R4 subunit generated with GRASP ([38]). Positively charged surface is colored blue and negatively charged red. The second subunit is white in a wormlike representation. Surfaces corresponding to R1 and R4 are marked.
  The above figures are reprinted by permission from Cell Press: Cell (1999, 98, 537-546) copyright 1999.  
  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.  
  19959814 A.Lin, A.Hokugo, J.Choi, and I.Nishimura (2010).
Small cytoskeleton-associated molecule, fibroblast growth factor receptor 1 oncogene partner 2/wound inducible transcript-3.0 (FGFR1OP2/wit3.0), facilitates fibroblast-driven wound closure.
  Am J Pathol, 176, 108-121.  
  20463852 C.G.Pontrello, and I.M.Ethell (2009).
Accelerators, Brakes, and Gears of Actin Dynamics in Dendritic Spines.
  Open Neurosci J, 3, 67-86.  
19141864 J.J.Ipsaro, L.Huang, and A.Mondragón (2009).
Structures of the spectrin-ankyrin interaction binding domains.
  Blood, 113, 5385-5393.
PDB codes: 3f57 3f59
19366376 M.Maeda, E.Asano, D.Ito, S.Ito, Y.Hasegawa, M.Hamaguchi, and T.Senga (2009).
Characterization of interaction between CLP36 and palladin.
  FEBS J, 276, 2775-2785.  
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.  
19830582 P.K.Luther (2009).
The vertebrate muscle Z-disc: sarcomere anchor for structure and signalling.
  J Muscle Res Cell Motil, 30, 171-185.  
19072330 Q.Li, and L.W.Fung (2009).
Structural and dynamic study of the tetramerization region of non-erythroid alpha-spectrin: a frayed helix revealed by site-directed spin labeling electron paramagnetic resonance.
  Biochemistry, 48, 206-215.  
19327143 T.Klaavuniemi, N.Alho, P.Hotulainen, A.Kelloniemi, H.Havukainen, P.Permi, S.Mattila, and J.Ylänne (2009).
Characterization of the interaction between Actinin-Associated LIM Protein (ALP) and the rod domain of alpha-actinin.
  BMC Cell Biol, 10, 22.  
19229108 Y.Lai, G.D.Thomas, Y.Yue, H.T.Yang, D.Li, C.Long, L.Judge, B.Bostick, J.S.Chamberlain, R.L.Terjung, and D.Duan (2009).
Dystrophins carrying spectrin-like repeats 16 and 17 anchor nNOS to the sarcolemma and enhance exercise performance in a mouse model of muscular dystrophy.
  J Clin Invest, 119, 624-635.  
18617516 I.Talior-Volodarsky, V.K.Randhawa, H.Zaid, and A.Klip (2008).
Alpha-actinin-4 is selectively required for insulin-induced GLUT4 translocation.
  J Biol Chem, 283, 25115-25123.  
18296101 M.Lorenzi, and M.Gimona (2008).
Synthetic actin-binding domains reveal compositional constraints for function.
  Int J Biochem Cell Biol, 40, 1806-1816.  
18059477 N.Pinotsis, S.Lange, J.C.Perriard, D.I.Svergun, and M.Wilmanns (2008).
Molecular basis of the C-terminal tail-to-tail assembly of the sarcomeric filament protein myomesin.
  EMBO J, 27, 253-264.
PDB code: 2r15
18815288 X.An, E.Gauthier, X.Zhang, X.Guo, D.J.Anstee, N.Mohandas, and J.A.Chasis (2008).
Adhesive activity of Lu glycoproteins is regulated by interaction with spectrin.
  Blood, 112, 5212-5218.  
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.  
17192394 C.P.Johnson, M.Gaetani, V.Ortiz, N.Bhasin, S.Harper, P.G.Gallagher, D.W.Speicher, and D.E.Discher (2007).
Pathogenic proline mutation in the linker between spectrin repeats: disease caused by spectrin unfolding.
  Blood, 109, 3538-3543.  
17294137 I.Ahmed, A.S.Ponery, A.Nur-E-Kamal, J.Kamal, A.S.Meshel, M.P.Sheetz, M.Schindler, and S.Meiners (2007).
Morphology, cytoskeletal organization, and myosin dynamics of mouse embryonic fibroblasts cultured on nanofibrillar surfaces.
  Mol Cell Biochem, 301, 241-249.  
17371879 K.Ojima, Y.Ono, N.Doi, K.Yoshioka, Y.Kawabata, S.Labeit, and H.Sorimachi (2007).
Myogenic stage, sarcomere length, and protease activity modulate localization of muscle-specific calpain.
  J Biol Chem, 282, 14493-14504.  
17085494 L.G.Randles, R.W.Rounsevell, and J.Clarke (2007).
Spectrin domains lose cooperativity in forced unfolding.
  Biophys J, 92, 571-577.  
17254972 M.E.Janson, R.Loughlin, I.Loïodice, C.Fu, D.Brunner, F.J.Nédélec, and P.T.Tran (2007).
Crosslinkers and motors organize dynamic microtubules to form stable bipolar arrays in fission yeast.
  Cell, 128, 357-368.  
17115122 M.Soncini, S.Vesentini, D.Ruffoni, M.Orsi, M.A.Deriu, and A.Redaelli (2007).
Mechanical response and conformational changes of alpha-actinin domains during unfolding: a molecular dynamics study.
  Biomech Model Mechanobiol, 6, 399-407.  
17925230 S.Mukhina, Y.L.Wang, and M.Murata-Hori (2007).
Alpha-actinin is required for tightly regulated remodeling of the actin cortical network during cytokinesis.
  Dev Cell, 13, 554-565.  
17867784 S.Paramore, G.S.Ayton, and G.A.Voth (2007).
Transient violations of the second law of thermodynamics in protein unfolding examined using synthetic atomic force microscopy and the fluctuation theorem.
  J Chem Phys, 127, 105105.  
  16569237 D.L.Scott, G.Diez, and W.H.Goldmann (2006).
Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data.
  Theor Biol Med Model, 3, 17.  
16464232 J.Kremerskothen, S.Kindler, I.Finger, S.Veltel, and A.Barnekow (2006).
Postsynaptic recruitment of Dendrin depends on both dendritic mRNA transport and synaptic anchoring.
  J Neurochem, 96, 1659-1666.  
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
16980305 S.Chakraborty, E.L.Reineke, M.Lam, X.Li, Y.Liu, C.Gao, S.Khurana, and H.Y.Kao (2006).
Alpha-actinin 4 potentiates myocyte enhancer factor-2 transcription activity by antagonizing histone deacetylase 7.
  J Biol Chem, 281, 35070-35080.  
16891371 S.Paramore, and G.A.Voth (2006).
Examining the influence of linkers and tertiary structure in the forced unfolding of multiple-repeat spectrin molecules.
  Biophys J, 91, 3436-3445.  
16227506 S.Paramore, G.S.Ayton, D.T.Mirijanian, and G.A.Voth (2006).
Extending a spectrin repeat unit. I: linear force-extension response.
  Biophys J, 90, 92.  
16227505 S.Paramore, G.S.Ayton, and G.A.Voth (2006).
Extending a spectrin repeat unit. II: rupture behavior.
  Biophys J, 90, 101-111.  
17014558 T.S.Ha (2006).
High glucose and advanced glycosylated end-products affect the expression of alpha-actinin-4 in glomerular epithelial cells.
  Nephrology (Carlton), 11, 435-441.  
16476728 X.An, X.Guo, X.Zhang, A.J.Baines, G.Debnath, D.Moyo, M.Salomao, N.Bhasin, C.Johnson, D.Discher, W.B.Gratzer, and N.Mohandas (2006).
Conformational stabilities of the structural repeats of erythroid spectrin and their functional implications.
  J Biol Chem, 281, 10527-10532.  
16043482 G.Baldini, A.M.Martelli, G.Tabellini, C.Horn, K.Machaca, P.Narducci, and G.Baldini (2005).
Rabphilin localizes with the cell actin cytoskeleton and stimulates association of granules with F-actin cross-linked by {alpha}-actinin.
  J Biol Chem, 280, 34974-34984.  
15841212 K.Asanuma, K.Kim, J.Oh, L.Giardino, S.Chabanis, C.Faul, J.Reiser, and P.Mundel (2005).
Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner.
  J Clin Invest, 115, 1188-1198.  
15988023 P.R.Bois, R.A.Borgon, C.Vonrhein, and T.Izard (2005).
Structural dynamics of alpha-actinin-vinculin interactions.
  Mol Cell Biol, 25, 6112-6122.
PDB code: 1ydi
15937186 V.Oganesyan, N.Oganesyan, P.D.Adams, J.Jancarik, H.A.Yokota, R.Kim, and S.H.Kim (2005).
Crystal structure of the "PhoU-like" phosphate uptake regulator from Aquifex aeolicus.
  J Bacteriol, 187, 4238-4244.
PDB codes: 1t72 1t8b
14992721 A.Shimada, M.Nyitrai, I.R.Vetter, D.Kühlmann, B.Bugyi, S.Narumiya, M.A.Geeves, and A.Wittinghofer (2004).
The core FH2 domain of diaphanous-related formins is an elongated actin binding protein that inhibits polymerization.
  Mol Cell, 13, 511-522.
PDB code: 1v9d
15062087 H.Kusunoki, R.I.MacDonald, and A.Mondragón (2004).
Structural insights into the stability and flexibility of unusual erythroid spectrin repeats.
  Structure, 12, 645-656.
PDB code: 1s35
15350170 K.R.Bowles, and N.E.Bowles (2004).
Genetics of inherited cardiomyopathies.
  Expert Rev Cardiovasc Ther, 2, 683-697.  
15152255 L.Lanzetti, A.Palamidessi, L.Areces, G.Scita, and P.P.Di Fiore (2004).
Rab5 is a signalling GTPase involved in actin remodelling by receptor tyrosine kinases.
  Nature, 429, 309-314.  
15056568 N.P.Lee, and C.Y.Cheng (2004).
Adaptors, junction dynamics, and spermatogenesis.
  Biol Reprod, 71, 392-404.  
14747656 R.I.MacDonald, and J.A.Cummings (2004).
Stabilities of folding of clustered, two-repeat fragments of spectrin reveal a potential hinge in the human erythroid spectrin tetramer.
  Proc Natl Acad Sci U S A, 101, 1502-1507.  
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.  
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.  
12589684 J.R.Henderson, P.Pomiès, C.Auffray, and M.C.Beckerle (2003).
ALP and MLP distribution during myofibrillogenesis in cultured cardiomyocytes.
  Cell Motil Cytoskeleton, 54, 254-265.  
14536023 M.Grynberg, L.Jaroszewski, and A.Godzik (2003).
Domain analysis of the tubulin cofactor system: a model for tubulin folding and dimerization.
  BMC Bioinformatics, 4, 46.  
12441356 M.M.Petit, S.M.Meulemans, and W.J.Van de Ven (2003).
The focal adhesion and nuclear targeting capacity of the LIM-containing lipoma-preferred partner (LPP) protein.
  J Biol Chem, 278, 2157-2168.  
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.  
12445285 F.Mami-Chouaib, H.Echchakir, G.Dorothée, I.Vergnon, and S.Chouaib (2002).
Antitumor cytotoxic T-lymphocyte response in human lung carcinoma: identification of a tumor-associated antigen.
  Immunol Rev, 188, 114-121.  
12142273 K.A.Clark, A.S.McElhinny, M.C.Beckerle, and C.C.Gregorio (2002).
Striated muscle cytoarchitecture: an intricate web of form and function.
  Annu Rev Cell Dev Biol, 18, 637-706.  
11948621 N.Kureishy, V.Sapountzi, S.Prag, N.Anilkumar, and J.C.Adams (2002).
Fascins, and their roles in cell structure and function.
  Bioessays, 24, 350-361.  
11781567 D.A.Calderwood, A.Huttenlocher, W.B.Kiosses, D.M.Rose, D.G.Woodside, M.A.Schwartz, and M.H.Ginsberg (2001).
Increased filamin binding to beta-integrin cytoplasmic domains inhibits cell migration.
  Nat Cell Biol, 3, 1060-1068.  
11298348 G.Mostoslavsky, R.Fischel, N.Yachimovich, Y.Yarkoni, E.Rosenmann, M.Monestier, M.Baniyash, and D.Eilat (2001).
Lupus anti-DNA autoantibodies cross-react with a glomerular structural protein: a case for tissue injury by molecular mimicry.
  Eur J Immunol, 31, 1221-1227.  
  11294907 J.Q.Wu, J.Bähler, and J.R.Pringle (2001).
Roles of a fimbrin and an alpha-actinin-like protein in fission yeast cell polarization and cytokinesis.
  Mol Biol Cell, 12, 1061-1077.  
11696561 Q.Zhou, P.H.Chu, C.Huang, C.F.Cheng, M.E.Martone, G.Knoll, G.D.Shelton, S.Evans, and J.Chen (2001).
Ablation of Cypher, a PDZ-LIM domain Z-line protein, causes a severe form of congenital myopathy.
  J Cell Biol, 155, 605-612.  
11226153 W.Kliche, S.Fujita-Becker, M.Kollmar, D.J.Manstein, and F.J.Kull (2001).
Structure of a genetically engineered molecular motor.
  EMBO J, 20, 40-46.
PDB code: 1g8x
10700177 J.M.Kaplan, S.H.Kim, K.N.North, H.Rennke, L.A.Correia, H.Q.Tong, B.J.Mathis, J.C.Rodríguez-Pérez, P.G.Allen, A.H.Beggs, and M.R.Pollak (2000).
Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis.
  Nat Genet, 24, 251-256.  
10931874 M.M.Parast, and C.A.Otey (2000).
Characterization of palladin, a novel protein localized to stress fibers and cell adhesions.
  J Cell Biol, 150, 643-656.  
11101506 P.Young, and M.Gautel (2000).
The interaction of titin and alpha-actinin is controlled by a phospholipid-regulated intramolecular pseudoligand mechanism.
  EMBO J, 19, 6331-6340.  
10753915 T.Vallenius, K.Luukko, and T.P.Mäkelä (2000).
CLP-36 PDZ-LIM protein associates with nonmuscle alpha-actinin-1 and alpha-actinin-4.
  J Biol Chem, 275, 11100-11105.  
10607557 A.McGough (1999).
How to build a molecular shock absorber.
  Curr Biol, 9, R887-R889.  
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.