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PDBsum entry 1hqv

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protein metals links
Apoptosis PDB id
1hqv
Jmol PyMol
Contents
Protein chain
178 a.a. *
Metals
_CA ×4
Waters ×51
* Residue conservation analysis
PDB id:
1hqv
Name: Apoptosis
Title: Structure of apoptosis-linked protein alg-2
Structure: Programmed cell death protein 6. Chain: a. Synonym: probable calcium-binding protein alg-2. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.30Å     R-factor:   0.250     R-free:   0.295
Authors: J.Jia,S.Tarabykina,C.Hansen,M.Berchtold,M.Cygler
Key ref:
J.Jia et al. (2001). Structure of apoptosis-linked protein ALG-2: insights into Ca2+-induced changes in penta-EF-hand proteins. Structure, 9, 267-275. PubMed id: 11525164 DOI: 10.1016/S0969-2126(01)00585-8
Date:
19-Dec-00     Release date:   02-May-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P12815  (PDCD6_MOUSE) -  Programmed cell death protein 6
Seq:
Struc:
191 a.a.
178 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     endoplasmic reticulum exit site   13 terms 
  Biological process     apoptotic process   21 terms 
  Biochemical function     protein binding     11 terms  

 

 
DOI no: 10.1016/S0969-2126(01)00585-8 Structure 9:267-275 (2001)
PubMed id: 11525164  
 
 
Structure of apoptosis-linked protein ALG-2: insights into Ca2+-induced changes in penta-EF-hand proteins.
J.Jia, S.Tarabykina, C.Hansen, M.Berchtold, M.Cygler.
 
  ABSTRACT  
 
BACKGROUND: The Ca2+ binding apoptosis-linked gene-2 (ALG-2) protein acts as a proapoptotic factor in a variety of cell lines and is required either downstream or independently of caspases for apoptosis to occur. ALG-2 belongs to the penta-EF-hand (PEF) protein family and has two high-affinity and one low-affinity Ca2+ binding sites. Like other PEF proteins, its N terminus contains a Gly/Pro-rich segment. Ca2+ binding is required for the interaction with the target protein, ALG-2 interacting protein 1 (AIP1). RESULTS: We present the 2.3 A resolution crystal structure of Ca2+-Ioaded des1-20ALG-2 (aa 21-191), which was obtained by limited proteolysis of recombinant ALG-2 with elastase. The molecule contains eight alpha helices that fold into five EF-hands, and, similar to other members of this protein family, the molecule forms dimers. Ca2+ ions bind to EF1, EF3, and, surprisingly, to EF5. In the related proteins calpain and grancalcin, the EF5 does not bind Ca2+ and is thought to primarily facilitate dimerization. Most importantly, the conformation of des1-20ALG-2 is significantly different from that of calpain and grancalcin. This difference can be described as a rigid body rotation of EF1-2 relative to EF4-5 and the dimer interface, with a hinge within the EF3 loop. An electron density, which is interpreted as a hydrophobic Gly/Pro-rich decapeptide that is possibly derived from the cleaved N terminus, was found in a hydrophobic cleft between these two halves of the molecule. CONCLUSIONS: A different relative orientation of the N- and C-terminal halves of des1-20ALG-2 in the presence of Ca2+ and the peptide as compared to other Ca2+loaded PEF proteins changes substantially the shape of the molecule, exposing a hydrophobic patch on the surface for peptide binding and a large cleft near the dimer interface. We postulate that the binding of a Gly/ Pro-rich peptide in the presence of Ca2+ induces a conformational rearrangement in ALG-2, and that this mechanism is common to other PEF proteins.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. View of the EF1 and EF5 Ca^2+ Binding Sites(a) Calcium binding to EF1.(b) Calcium binding to EF5.Dashed lines mark the contacts to the oxygen ligands. The figure was prepared with programs Molscript [37] and Raster3d [38]

 
  The above figure is reprinted by permission from Cell Press: Structure (2001, 9, 267-275) copyright 2001.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21103355 O.Gusev, Y.Nakahara, V.Vanyagina, L.Malutina, R.Cornette, T.Sakashita, N.Hamada, T.Kikawada, Y.Kobayashi, and T.Okuda (2010).
Anhydrobiosis-associated nuclear DNA damage and repair in the sleeping chironomid: linkage with radioresistance.
  PLoS One, 5, e14008.  
  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
18256029 H.Shibata, H.Suzuki, T.Kakiuchi, T.Inuzuka, H.Yoshida, T.Mizuno, and M.Maki (2008).
Identification of Alix-type and Non-Alix-type ALG-2-binding sites in human phospholipid scramblase 3: differential binding to an alternatively spliced isoform and amino acid-substituted mutants.
  J Biol Chem, 283, 9623-9632.  
  18997320 H.Suzuki, M.Kawasaki, T.Kakiuchi, H.Shibata, S.Wakatsuki, and M.Maki (2008).
Crystallization and X-ray diffraction analysis of N-terminally truncated human ALG-2.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 974-977.
PDB codes: 2zrs 2zrt
17889823 I.Draeby, Y.L.Woods, J.M.la Cour, J.Mollerup, J.C.Bourdon, and M.W.Berchtold (2007).
The calcium binding protein ALG-2 binds and stabilizes Scotin, a p53-inducible gene product localized at the endoplasmic reticulum membrane.
  Arch Biochem Biophys, 467, 87-94.  
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.  
16569194 M.Wiens, S.I.Belikov, O.V.Kaluzhnaya, H.C.Schröder, B.Hamer, S.Perovic-Ottstadt, A.Borejko, B.Luthringer, I.M.Müller, and W.E.Müller (2006).
Axial (apical-basal) expression of pro-apoptotic and pro-survival genes in the lake baikal demosponge Lubomirskia baicalensis.
  DNA Cell Biol, 25, 152-164.  
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.  
15487944 M.A.Peñalva, and H.N.Arst (2004).
Recent advances in the characterization of ambient pH regulation of gene expression in filamentous fungi and yeasts.
  Annu Rev Microbiol, 58, 425-451.  
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
11927596 L.Aubry, S.Mattei, B.Blot, R.Sadoul, M.Satre, and G.Klein (2002).
Biochemical characterization of two analogues of the apoptosis-linked gene 2 protein in Dictyostelium discoideum and interaction with a physiological partner in mammals, murine Alix.
  J Biol Chem, 277, 21947-21954.  
11717497 J.Jia, N.Borregaard, K.Lollike, and M.Cygler (2001).
Structure of Ca(2+)-loaded human grancalcin.
  Acta Crystallogr D Biol Crystallogr, 57, 1843-1849.
PDB codes: 1k94 1k95
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.

 

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