PDBsum entry 2zne

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protein metals Protein-protein interface(s) links
Apoptosis PDB id
Protein chains
168 a.a. *
15 a.a. *
12 a.a. *
_NA ×2
_ZN ×8
Waters ×68
* Residue conservation analysis
PDB id:
Name: Apoptosis
Title: Crystal structure of zn2+-bound form of des3-23alg-2 complexed with alix abs peptide
Structure: Programmed cell death protein 6. Chain: a, b. Fragment: residues 2-191. Synonym: apoptosis-linked gene 2 protein, probable calcium- binding protein alg-2. Engineered: yes. 16-meric peptide from programmed cell death 6- interacting protein. Chain: c, d.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pdcd6, alg2. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: chemical synthesis. This sequence occurs naturally in humans.
2.20Å     R-factor:   0.225     R-free:   0.274
Authors: H.Suzuki,M.Kawasaki,T.Inuzuka,T.Kakiuchi,H.Shibata, S.Wakatsuki,M.Maki
Key ref:
H.Suzuki et al. (2008). Structural basis for Ca2+ -dependent formation of ALG-2/Alix peptide complex: Ca2+/EF3-driven arginine switch mechanism. Structure, 16, 1562-1573. PubMed id: 18940611 DOI: 10.1016/j.str.2008.07.012
22-Apr-08     Release date:   09-Sep-08    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
O75340  (PDCD6_HUMAN) -  Programmed cell death protein 6
191 a.a.
168 a.a.
Protein chain
Pfam   ArchSchema ?
Q8WUM4  (PDC6I_HUMAN) -  Programmed cell death 6-interacting protein
868 a.a.
15 a.a.*
Protein chain
Pfam   ArchSchema ?
Q8WUM4  (PDC6I_HUMAN) -  Programmed cell death 6-interacting protein
868 a.a.
12 a.a.
Key:    PfamA 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: 10.1016/j.str.2008.07.012 Structure 16:1562-1573 (2008)
PubMed id: 18940611  
Structural basis for Ca2+ -dependent formation of ALG-2/Alix peptide complex: Ca2+/EF3-driven arginine switch mechanism.
H.Suzuki, M.Kawasaki, T.Inuzuka, M.Okumura, T.Kakiuchi, H.Shibata, S.Wakatsuki, M.Maki.
ALG-2 belongs to the penta-EF-hand (PEF) protein family and interacts with various intracellular proteins, such as Alix and TSG101, that are involved in endosomal sorting and HIV budding. Through X-ray crystallography, we solved the structures of Ca(2+)-free and -bound forms of N-terminally truncated human ALG-2 (des3-20ALG-2), Zn(2+)-bound form of full-length ALG-2, and the structure of the complex between des3-23ALG-2 and the peptide corresponding to Alix799-814 in Zn(2+)-bound form. Binding of Ca(2+) to EF3 enables the side chain of Arg125, present in the loop connecting EF3 and EF4, to move enough to make a primary hydrophobic pocket accessible to the critical PPYP motif, which partially overlaps with the GPP motif for the binding of Cep55 (centrosome protein 55 kDa). Based on these results, together with the results of in vitro binding assay with mutant ALG-2 and Alix proteins, we propose a Ca(2+)/EF3-driven arginine switch mechanism for ALG-2 binding to Alix.
  Selected figure(s)  
Figure 1.
Figure 1. Schematic Representations of ALG-2 and Alix
Human ALG-2 has a Gly/Pro-rich N-terminal region followed by the PEF domain containing five EF-hands (EF1–EF5) with eight α helices (α1–α8). The first and second helices in each EF hand are alternatively named, for instance, helix E1 and helix F1, respectively. An alternatively spliced isoform (lacking Gly121-Phe122) is designated ALG-2^ΔGF122 in this article. Recombinant proteins of full-length ALG-2 and two types of N-terminal deletion mutants (des3-20ALG-2 and des3-23ALG-2) were crystallized. Alix has three distinct domains, named Bro1, V, and Pro-rich. A 16-mer synthetic oligopeptide of the ABS in Alix (Alix ABS peptide) was used for cocrystallization.
Figure 2.
Figure 2. Comparison of Ca^2+-Free and Ca^2+-Bound Forms and Zn^2+-Bound Form of ALG-2
(A–C) Structures of EF1 (A), EF3 (B), and EF5 (C) of Ca^2+-free form (cyan) and Ca^2+-bound form (magenta) of des3-20ALG-2 and Zn^2+-bound form (green) of full-length ALG-2 are superimposed and shown in ribbon representation in side views and top views by aligning helices of (A) α1 (E1), (B) α4 (E3), and (C) α7 (E5), respectively, with the secondary structure matching program in COOT. Calcium atoms and zinc atoms are shown as yellow spheres and gray spheres, respectively.
(D) Overall structures of dimeric ALG-2 molecules in the three forms are aligned at α7 of molecule A and shown in wire presentation. The N-terminal Gly/Pro-rich region is invisible.
  The above figures are reprinted by permission from Cell Press: Structure (2008, 16, 1562-1573) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21122810 A.Janowicz, M.Michalak, and J.Krebs (2011).
Stress induced subcellular distribution of ALG-2, RBM22 and hSlu7.
  Biochim Biophys Acta, 1813, 1045-1049.  
20834162 H.Shibata, T.Inuzuka, H.Yoshida, H.Sugiura, I.Wada, and M.Maki (2010).
The ALG-2 binding site in Sec31A influences the retention kinetics of Sec31A at the endoplasmic reticulum exit sites as revealed by live-cell time-lapse imaging.
  Biosci Biotechnol Biochem, 74, 1819-1826.  
  20653365 J.H.Hurley (2010).
The ESCRT complexes.
  Crit Rev Biochem Mol Biol, 45, 463-487.  
20017116 R.L.Rich, and D.G.Myszka (2010).
Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'.
  J Mol Recognit, 23, 1.  
  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
19523902 R.Pires, B.Hartlieb, L.Signor, G.Schoehn, S.Lata, M.Roessle, C.Moriscot, S.Popov, A.Hinz, M.Jamin, V.Boyer, R.Sadoul, E.Forest, D.I.Svergun, H.G.Göttlinger, and W.Weissenhorn (2009).
A crescent-shaped ALIX dimer targets ESCRT-III CHMP4 filaments.
  Structure, 17, 843-856.  
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.