PDBsum entry 1aj5

Calcium-binding protein

PDB id

1aj5

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Contents

			Protein chains

					173 a.a. *

			Waters ×120

* Residue conservation analysis

PDB id:

1aj5

Links

Name:

Calcium-binding protein

Title:

Calpain domain vi apo

Structure:

Calpain. Chain: a, b. Fragment: small regulatory subunit, domain vi, met 87 - ser 270. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Strain: bl21 (de3). Cell_line: bl21. Organ: liver. Gene: capn4. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Hetero-Dimer (from PDB file)

Resolution:

2.30Å

R-factor:

0.220

R-free:

0.306

Authors:

M.Cygler,P.Grochulski,H.Blanchard

Key ref:

H.Blanchard et al. (1997). Structure of a calpain Ca(2+)-binding domain reveals a novel EF-hand and Ca(2+)-induced conformational changes. Nat Struct Biol, 4, 532-538. PubMed id: 9228945

Date:

15-May-97

Release date:

20-May-98

PROCHECK

	Headers

	References

Protein chains

Q64537 (CPNS1_RAT) - Calpain small subunit 1 from Rattus norvegicus

Seq: Struc:					270 a.a. 173 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.?

[IntEnz] [ExPASy] [KEGG] [BRENDA]

	Nat Struct Biol 4:532-538 (1997)
PubMed id: 9228945

Structure of a calpain Ca(2+)-binding domain reveals a novel EF-hand and Ca(2+)-induced conformational changes.
H.Blanchard, P.Grochulski, Y.Li, J.S.Arthur, P.L.Davies, J.S.Elce, M.Cygler.

ABSTRACT

The crystal structure of a Ca(2+)-binding domain (dVI) of rat m-calpain has been determined at 2.3 A resolution, both with and without bound Ca2+. The structures reveal a unique fold incorporating five EF-hand motifs per monomer, three of which bind calcium at physiological calcium concentrations, with one showing a novel EF-hand coordination pattern. This investigation gives us a first view of the calcium-induced conformational changes, and consequently an insight into the mechanism of calcium induced activation in calpain. The crystal structures reveal a dVI homodimer which provides a preliminary model for the subunit dimerization in calpain.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21508973

S.J.Storr, N.O.Carragher, M.C.Frame, T.Parr, and S.G.Martin (2011).
The calpain system and cancer.

Nat Rev Cancer, 11, 364-374.

20298697

C.Zamparelli, N.Macquaide, G.Colotti, D.Verzili, T.Seidler, G.L.Smith, and E.Chiancone (2010).
Activation of the cardiac Na(+)-Ca(2+) exchanger by sorcin via the interaction of the respective Ca(2+)-binding domains.

J Mol Cell Cardiol, 49, 132-141.

19864426

T.Oda, H.Hashimoto, N.Kuwabara, S.Akashi, K.Hayashi, C.Kojima, H.L.Wong, T.Kawasaki, K.Shimamoto, M.Sato, and T.Shimizu (2010).
Structure of the N-terminal regulatory domain of a plant NADPH oxidase and its functional implications.

J Biol Chem, 285, 1435-1445.

PDB code:

3a8r

19164769

I.Russo, A.Oksman, B.Vaupel, and D.E.Goldberg (2009).
A calpain unique to alveolates is essential in Plasmodium falciparum and its knockdown reveals an involvement in pre-S-phase development.

Proc Natl Acad Sci U S A, 106, 1554-1559.

18793761

D.E.Croall, L.M.Vanhooser, and R.E.Cashon (2008).
Detecting the active conformation of calpain with calpastatin-based reagents.

Biochim Biophys Acta, 1784, 1676-1686.

18280495

E.Johnson, L.Bruschweiler-Li, S.A.Showalter, G.W.Vuister, F.Zhang, and R.Brüschweiler (2008).
Structure and dynamics of Ca2+-binding domain 1 of the Na+/Ca2+ exchanger in the presence and in the absence of Ca2+.

J Mol Biol, 377, 945-955.

18686046

P.S.Vosler, C.S.Brennan, and J.Chen (2008).
Calpain-mediated signaling mechanisms in neuronal injury and neurodegeneration.

Mol Neurobiol, 38, 78.

19020622

T.Moldoveanu, K.Gehring, and D.R.Green (2008).
Concerted multi-pronged attack by calpastatin to occlude the catalytic cleft of heterodimeric calpains.

Nature, 456, 404-408.

PDB code:

3df0

17640275

S.Vernarecci, G.Colotti, P.Ornaghi, E.Schiebel, E.Chiancone, and P.Filetici (2007).
The yeast penta-EF protein Pef1p is involved in cation-dependent budding and cell polarization.

Mol Microbiol, 65, 1122-1138.

16623703

M.Averna, R.Stifanese, R.De Tullio, E.Defranchi, F.Salamino, E.Melloni, and S.Pontremoli (2006).
Interaction between catalytically inactive calpain and calpastatin. Evidence for its occurrence in stimulated cells.

FEBS J, 273, 1660-1668.

14976200

A.Alexa, Z.Bozóky, A.Farkas, P.Tompa, and P.Friedrich (2004).
Contribution of distinct structural elements to activation of calpain by Ca2+ ions.

J Biol Chem, 279, 20118-20126.

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.

14749380

T.Franz, L.Winckler, T.Boehm, and T.N.Dear (2004).
Capn5 is expressed in a subset of T cells and is dispensable for development.

Mol Cell Biol, 24, 1649-1654.

14579356

E.K.Leinala, J.S.Arthur, P.Grochulski, P.L.Davies, J.S.Elce, and Z.Jia (2003).
A second binding site revealed by C-terminal truncation of calpain small subunit, a penta-EF-hand protein.

Proteins, 53, 649-655.

PDB code:

1np8

14656436

G.P.Pal, T.De Veyra, J.S.Elce, and Z.Jia (2003).
Crystal structure of a micro-like calpain reveals a partially activated conformation with low Ca2+ requirement.

Structure, 11, 1521-1526.

PDB code:

1qxp

12711611

M.Mella, G.Colotti, C.Zamparelli, D.Verzili, A.Ilari, and E.Chiancone (2003).
Information transfer in the penta-EF-hand protein sorcin does not operate via the canonical structural/functional pairing. A study with site-specific mutants.

J Biol Chem, 278, 24921-24928.

12517342

W.Iwasaki, H.Sasaki, A.Nakamura, K.Kohama, and M.Tanokura (2003).
Metal-free and Ca2+-bound structures of a multidomain EF-hand protein, CBP40, from the lower eukaryote Physarum polycephalum.

Structure, 11, 75-85.

PDB codes:

1ij5 1ij6

14500891

Z.Mucsi, F.Hudecz, M.Hollósi, P.Tompa, and P.Friedrich (2003).
Binding-induced folding transitions in calpastatin subdomains A and C.

Protein Sci, 12, 2327-2336.

12437134

D.Reverter, M.Braun, C.Fernandez-Catalan, S.Strobl, H.Sorimachi, and W.Bode (2002).
Flexibility analysis and structure comparison of two crystal forms of calcium-free human m-calpain.

Biol Chem, 383, 1415-1422.

12189137

E.Dainese, R.Minafra, A.Sabatucci, P.Vachette, E.Melloni, and I.Cozzani (2002).
Conformational changes of calpain from human erythrocytes in the presence of Ca2+.

J Biol Chem, 277, 40296-40301.

11796727

T.Maruoka, Y.Nagasoe, S.Inoue, Y.Mori, J.Goto, M.Ikeda, and H.Iida (2002).
Essential hydrophilic carboxyl-terminal regions including cysteine residues of the yeast stretch-activated calcium-permeable channel Mid1.

J Biol Chem, 277, 11645-11652.

11258679

B.G.Díaz, S.Gross, I.Assfalg-Machleidt, D.Pfeiler, N.Gollmitzer, D.Gabrijelcic-Geiger, M.T.Stubbs, H.Fritz, E.A.Auerswald, and W.Machleidt (2001).
Cystatins as calpain inhibitors: engineered chicken cystatin- and stefin B-kininogen domain 2 hybrids support a cystatin-like mode of interaction with the catalytic subunit of mu-calpain.

Biol Chem, 382, 97.

11517928

D.Reverter, S.Strobl, C.Fernandez-Catalan, H.Sorimachi, K.Suzuki, and W.Bode (2001).
Structural basis for possible calcium-induced activation mechanisms of calpains.

Biol Chem, 382, 753-766.

11525164

J.Jia, S.Tarabykina, C.Hansen, M.Berchtold, and M.Cygler (2001).
Structure of apoptosis-linked protein ALG-2: insights into Ca2+-induced changes in penta-EF-hand proteins.

Structure, 9, 267-275.

PDB code:

1hqv

11316872

M.Håkansson, A.Svensson, J.Fast, and S.Linse (2001).
An extended hydrophobic core induces EF-hand swapping.

Protein Sci, 10, 927-933.

PDB code:

1ht9

11342050

T.Moldoveanu, C.M.Hosfield, Z.Jia, J.S.Elce, and P.L.Davies (2001).
Ca(2+)-induced structural changes in rat m-calpain revealed by partial proteolysis.

Biochim Biophys Acta, 1545, 245-254.

11714909

X.Xie, M.D.Dwyer, L.Swenson, M.H.Parker, and M.C.Botfield (2001).
Crystal structure of calcium-free human sorcin: a member of the penta-EF-hand protein family.

Protein Sci, 10, 2419-2425.

PDB code:

1juo

11114499

A.Lewit-Bentley, and S.Réty (2000).
EF-hand calcium-binding proteins.

Curr Opin Struct Biol, 10, 637-643.

10651630

C.Zamparelli, A.Ilari, D.Verzili, L.Giangiacomo, G.Colotti, S.Pascarella, and E.Chiancone (2000).
Structure-function relationships in sorcin, a member of the penta EF-hand family. Interaction of sorcin fragments with the ryanodine receptor and an Escherichia coli model system.

Biochemistry, 39, 658-666.

10825211

J.S.Arthur, J.S.Elce, C.Hegadorn, K.Williams, and P.A.Greer (2000).
Disruption of the murine calpain small subunit gene, Capn4: calpain is essential for embryonic development but not for cell growth and division.

Mol Cell Biol, 20, 4474-4481.

10783162

S.B.Sokol, and P.E.Kuwabara (2000).
Proteolysis in Caenorhabditis elegans sex determination: cleavage of TRA-2A by TRA-3.

Genes Dev, 14, 901-906.

10639123

S.Strobl, C.Fernandez-Catalan, M.Braun, R.Huber, H.Masumoto, K.Nakagawa, A.Irie, H.Sorimachi, G.Bourenkow, H.Bartunik, K.Suzuki, and W.Bode (2000).
The crystal structure of calcium-free human m-calpain suggests an electrostatic switch mechanism for activation by calcium.

Proc Natl Acad Sci U S A, 97, 588-592.

PDB codes:

1dkv 1kfu 1kfx

10744743

S.Tarabykina, A.L.Møller, I.Durussel, J.Cox, and M.W.Berchtold (2000).
Two forms of the apoptosis-linked protein ALG-2 with different Ca(2+) affinities and target recognition.

J Biol Chem, 275, 10514-10518.

11152121

T.Berggård, E.Thulin, K.S.Akerfeldt, and S.Linse (2000).
Fragment complementation of calbindin D28k.

Protein Sci, 9, 2094-2108.

10601010

C.M.Hosfield, J.S.Elce, P.L.Davies, and Z.Jia (1999).
Crystal structure of calpain reveals the structural basis for Ca(2+)-dependent protease activity and a novel mode of enzyme activation.

EMBO J, 18, 6880-6889.

PDB code:

1df0

10591109

K.L.Yap, J.B.Ames, M.B.Swindells, and M.Ikura (1999).
Diversity of conformational states and changes within the EF-hand protein superfamily.

Proteins, 37, 499-507.

10360947

K.W.Lo, Q.Zhang, M.Li, and M.Zhang (1999).
Apoptosis-linked gene product ALG-2 is a new member of the calpain small subunit subfamily of Ca2+-binding proteins.

Biochemistry, 38, 7498-7508.

10545326

M.S.Cates, M.B.Berry, E.L.Ho, Q.Li, J.D.Potter, and G.N.Phillips (1999).
Metal-ion affinity and specificity in EF-hand proteins: coordination geometry and domain plasticity in parvalbumin.

Structure, 7, 1269-1278.

PDB codes:

1b8c 1b8l 1b8r 1b9a

10491581

S.L.Chan, and M.P.Mattson (1999).
Caspase and calpain substrates: roles in synaptic plasticity and cell death.

J Neurosci Res, 58, 167-190.

9524069

H.J.Lee, H.Sorimachi, S.Y.Jeong, S.Ishiura, and K.Suzuki (1998).
Molecular cloning and characterization of a novel tissue-specific calpain predominantly expressed in the digestive tract.

Biol Chem, 379, 175-183.

9667926

J.Evenäs, A.Malmendal, and S.Forsén (1998).
Calcium.

Curr Opin Chem Biol, 2, 293-302.

9593689

J.J.Chen, Y.Hong, E.Rustamzadeh, J.D.Baleja, and E.J.Androphy (1998).
Identification of an alpha helical motif sufficient for association with papillomavirus E6.

J Biol Chem, 273, 13537-13544.

9774740

J.S.Arthur, P.A.Greer, and J.S.Elce (1998).
Structure of the mouse calpain small subunit gene.

Biochim Biophys Acta, 1388, 247-252.

9585577

R.R.Biekofsky, S.R.Martin, J.P.Browne, P.M.Bayley, and J.Feeney (1998).
Ca2+ coordination to backbone carbonyl oxygen atoms in calmodulin and other EF-hand proteins: 15N chemical shifts as probes for monitoring individual-site Ca2+ coordination.

Biochemistry, 37, 7617-7629.

9642272

Y.Ono, H.Shimada, H.Sorimachi, I.Richard, T.C.Saido, J.S.Beckmann, S.Ishiura, and K.Suzuki (1998).
Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A.

J Biol Chem, 273, 17073-17078.

9345628

K.Moffat, and Z.Ren (1997).
Synchrotron radiation applications to macromolecular crystallography.

Curr Opin Struct Biol, 7, 689-696.

9385641

S.Linse, E.Thulin, L.K.Gifford, D.Radzewsky, J.Hagan, R.R.Wilk, and K.S.Akerfeldt (1997).
Domain organization of calbindin D28k as determined from the association of six synthetic EF-hand fragments.

Protein Sci, 6, 2385-2396.

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.