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PDBsum entry 1f4o

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protein metals Protein-protein interface(s) links
Metal transport PDB id
1f4o
Jmol
Contents
Protein chain
165 a.a. *
Metals
_CA
Waters ×53
* Residue conservation analysis
PDB id:
1f4o
Name: Metal transport
Title: Crystal structure of grancalcin with bound calcium
Structure: Grancalcin. Chain: a, b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.50Å     R-factor:   0.228     R-free:   0.284
Authors: J.Jia,Q.Han,N.Borregaard,K.Lollike,M.Cygler
Key ref:
J.Jia et al. (2000). Crystal structure of human grancalcin, a member of the penta-EF-hand protein family. J Mol Biol, 300, 1271-1281. PubMed id: 10903868 DOI: 10.1006/jmbi.2000.3925
Date:
08-Jun-00     Release date:   27-Sep-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam  
P28676  (GRAN_HUMAN) -  Grancalcin
Seq:
Struc:
217 a.a.
165 a.a.*
Key:    Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

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

 

 
DOI no: 10.1006/jmbi.2000.3925 J Mol Biol 300:1271-1281 (2000)
PubMed id: 10903868  
 
 
Crystal structure of human grancalcin, a member of the penta-EF-hand protein family.
J.Jia, Q.Han, N.Borregaard, K.Lollike, M.Cygler.
 
  ABSTRACT  
 
Grancalcin is a Ca(2+)-binding protein expressed at high level in neutrophils. It belongs to the PEF family, proteins containing five EF-hand motifs and which are known to associate with membranes in Ca(2+)-dependent manner. Prototypic members of this family are Ca(2+)-binding domains of calpain. Our recent finding that grancalcin interacts with L-plastin, a protein known to have actin bundling activity, suggests that grancalcin may play a role in regulation of adherence and migration of neutrophils. The structure of human grancalcin has been determined at 1.9 A resolution in the absence of calcium (R-factor of 0.212 and R-free of 0.249) and at 2. 5 A resolution in the presence of calcium (R-factor of 0.226 and R-free of 0.281). The molecule is predominantly alpha-helical: it contains eight alpha-helices and only two short stretches of two-stranded beta-sheets between the loops of paired EF-hands. Grancalcin forms dimers through the association of the unpaired EF5 hands in a manner similar to that observed in calpain, confirming this mode of association as a paradigm for the PEF family. Only one Ca(2+) was found per dimer under crystallization conditions that included CaCl(2). This cation binds to EF3 in one molecule, while this site in the second molecule of the dimer is unoccupied. This unoccupied site shows higher mobility. The structure determined in the presence of calcium, although does not represent a fully Ca(2+)-loaded form, suggests that calcium induces rather small conformational rearrangements. Comparison with calpain suggests further that the relatively small magnitude of conformational changes invoked by calcium alone may be a characteristic feature of the PEF family. Moreover, the largest differences are localized to the EF1, thus supporting the notion that calcium signaling occurs through this portion of the molecule and that it may involve the N-terminal Gly/Pro rich segment. Electrostatic potential distribution shows significant differences between grancalcin and calpain domain VI demonstrating their distinct character.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. EF-hands of grancalcin and their comparison with calpain dVI. Grancalcin is shown in dark lines and calpain in light gray, Ca^2+ is shown as gray sphere connected by dashed lines to its ligands. (a) Superposition of EF1 of grancalcin and Ca^2+-bound EF1 of calpain dVI. Only the C-terminal part of the loop and helix F1 were used for superposition. The Ca^2+ of calpain is shown as a sphere and the dashed lines mark its ligands. The two small gray spheres are water molecules liganding calcium. (b) Superposition of EF2 from grancalcin and calpain domain VI. Note that in grancalcin the usual glutamate in position -Z is replaced by Ala113. (c) Comparison of Ca^2+-bound (dark) and Ca^2+-free EF3 from the Ca-grancalcin (light). (d) Superposition of EF5 of grancalcin and calpain dVI.
Figure 4.
Figure 4. (a) The stereo view of C^a tracing of grancalcin dimer (blue) with a superimposed domain VI of rat calpain (magenta). The view is along the symmetry axis of the dimer with the EF1 near the viewer. The main difference between the two proteins is in the positioning of EF1. (b) Electrostatic potential for grancalcin dimer, same view as above. (c) Electrostatic potential for calpain dVI in the same orientation as grancalcin.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 300, 1271-1281) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20594377 I.R.Gizer, C.L.Ehlers, C.Vieten, K.L.Seaton-Smith, H.S.Feiler, J.V.Lee, S.K.Segall, D.A.Gilder, and K.C.Wilhelmsen (2011).
Linkage scan of nicotine dependence in the University of California, San Francisco (UCSF) Family Alcoholism Study.
  Psychol Med, 41, 799-808.  
  20691033 T.Inuzuka, H.Suzuki, M.Kawasaki, H.Shibata, S.Wakatsuki, and M.Maki (2010).
Molecular basis for defect in Alix-binding by alternatively spliced isoform of ALG-2 (ALG-2DeltaGF122) and structural roles of F122 in target recognition.
  BMC Struct Biol, 10, 25.
PDB codes: 3aaj 3aak
18559337 J.N.Wingard, J.Ladner, M.Vanarotti, A.J.Fisher, H.Robinson, K.T.Buchanan, D.M.Engman, and J.B.Ames (2008).
Structural Insights into Membrane Targeting by the Flagellar Calcium-binding Protein (FCaBP), a Myristoylated and Palmitoylated Calcium Sensor in Trypanosoma cruzi.
  J Biol Chem, 283, 23388-23396.
PDB code: 3cs1
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.  
15366927 L.Subramanian, J.W.Crabb, J.Cox, I.Durussel, T.M.Walker, P.R.van Ginkel, S.Bhattacharya, J.M.Dellaria, K.Palczewski, and A.S.Polans (2004).
Ca2+ binding to EF hands 1 and 3 is essential for the interaction of apoptosis-linked gene-2 with Alix/AIP1 in ocular melanoma.
  Biochemistry, 43, 11175-11186.  
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
12529388 J.Roes, B.K.Choi, D.Power, P.Xu, and A.W.Segal (2003).
Granulocyte function in grancalcin-deficient mice.
  Mol Cell Biol, 23, 826-830.  
12754254 M.B.Meyers, A.Fischer, Y.J.Sun, C.M.Lopes, T.Rohacs, T.Y.Nakamura, Y.Y.Zhou, P.C.Lee, R.A.Altschuld, S.A.McCune, W.A.Coetzee, and G.I.Fishman (2003).
Sorcin regulates excitation-contraction coupling in the heart.
  J Biol Chem, 278, 28865-28871.  
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
11468406 F.Wu, M.Zhang, and W.Gong (2001).
Crystallization and preliminary crystallographic studies of an apoptosis-linked calcium-binding protein ALG-2.
  Acta Crystallogr D Biol Crystallogr, 57, 1162-1163.  
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
11375509 V.Nastopoulos, A.Ilari, G.Colotti, C.Zamparelli, D.Verzili, E.Chiancone, and D.Tsernoglou (2001).
Two different crystal forms of sorcin, a penta-EF-hand Ca2+-binding protein.
  Acta Crystallogr D Biol Crystallogr, 57, 862-864.  
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
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.