PDBsum entry 1aei

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protein metals Protein-protein interface(s) links
Calcium/phospholipid-binding PDB id
Protein chains
(+ 0 more) 315 a.a. *
_CA ×24
* Residue conservation analysis
PDB id:
Name: Calcium/phospholipid-binding
Title: Crystal structure of the annexin xii hexamer
Structure: Annexin xii. Chain: a, b, c, d, e, f. Engineered: yes
Source: Hydra vulgaris. Organism_taxid: 6087. Cell: battery cell. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Hexamer (from PDB file)
2.80Å     R-factor:   0.236     R-free:   0.278
Authors: H.Luecke,B.T.Chang,W.S.Mailliard,D.D.Schlaepfer,H.T.Haigler
Key ref: H.Luecke et al. (1995). Crystal structure of the annexin XII hexamer and implications for bilayer insertion. Nature, 378, 512-515. PubMed id: 7477411
23-Sep-95     Release date:   20-Aug-97    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P26256  (ANX12_HYDVU) -  Annexin-B12
316 a.a.
315 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     calcium-dependent phospholipid binding     2 terms  


Nature 378:512-515 (1995)
PubMed id: 7477411  
Crystal structure of the annexin XII hexamer and implications for bilayer insertion.
H.Luecke, B.T.Chang, W.S.Mailliard, D.D.Schlaepfer, H.T.Haigler.
Annexins are a family of calcium- and phospholipid-binding proteins implicated in a number of biological processes including membrane fusion and ion channel formation. The crystal structure of the annexin XII hexamer, refined at 2.8 A resolution, forms a concave disk with 3-2 symmetry, about 100 A in diameter and 70 A thick with a central hydrophilic pore. Six intermolecular Ca2+ ions are involved in hexamer formation. An additional 18 Ca2+ ions are located on the perimeter of the disk, accessible only from the side of the hexameric disk. On the basis of the hexamer structure we propose here a new mode of protein-phospholipid bilayer interaction that is distinct from the hydrophobic insertion of typical membrane proteins. This speculative model postulates the Ca(2+)-dependent insertion of the hydrophilic annexin XII hexamer into phospholipid bilayers with local reorientation of the bilayer phospholipids.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19966809 Y.E.Kim, J.Chen, J.R.Chan, and R.Langen (2010).
Engineering a polarity-sensitive biosensor for time-lapse imaging of apoptotic processes and degeneration.
  Nat Methods, 7, 67-73.  
20671723 Y.E.Kim, J.Chen, R.Langen, and J.R.Chan (2010).
Monitoring apoptosis and neuronal degeneration by real-time detection of phosphatidylserine externalization using a polarity-sensitive indicator of viability and apoptosis.
  Nat Protoc, 5, 1396-1405.  
19888325 C.Tortiglione, A.Quarta, M.A.Malvindi, A.Tino, and T.Pellegrino (2009).
Fluorescent nanocrystals reveal regulated portals of entry into and between the cells of Hydra.
  PLoS One, 4, e7698.  
19381436 K.Monastyrskaya, E.B.Babiychuk, and A.Draeger (2009).
The annexins: spatial and temporal coordination of signaling events during cellular stress.
  Cell Mol Life Sci, 66, 2623-2642.  
18256316 W.G.Hill, S.Meyers, M.von Bodungen, G.Apodaca, J.R.Dedman, M.A.Kaetzel, and M.L.Zeidel (2008).
Studies on localization and function of annexin A4a within urinary bladder epithelium using a mouse knockout model.
  Am J Physiol Renal Physiol, 294, F919-F927.  
  19279706 K.L.Massé, R.J.Collins, S.Bhamra, R.A.Seville, and E.A.Jones (2007).
Anxa4 Genes are Expressed in Distinct Organ Systems in Xenopus laevis and tropicalis But are Functionally Conserved.
  Organogenesis, 3, 83-92.  
17267400 T.Fischer, L.Lu, H.T.Haigler, and R.Langen (2007).
Annexin B12 is a sensor of membrane curvature and undergoes major curvature-dependent structural changes.
  J Biol Chem, 282, 9996.  
15975928 Y.E.Kim, J.M.Isas, H.T.Haigler, and R.Langen (2005).
A helical hairpin region of soluble annexin B12 refolds and forms a continuous transmembrane helix at mildly acidic pH.
  J Biol Chem, 280, 32398-32404.  
15143059 J.M.Isas, R.Langen, W.L.Hubbell, and H.T.Haigler (2004).
Structure and dynamics of a helical hairpin that mediates calcium-dependent membrane binding of annexin B12.
  J Biol Chem, 279, 32492-32498.  
15298924 M.Golczak, A.Kirilenko, J.Bandorowicz-Pikula, B.Desbat, and S.Pikula (2004).
Structure of human annexin a6 at the air-water interface and in a membrane-bound state.
  Biophys J, 87, 1215-1226.  
15280367 M.Jin, C.Smith, H.Y.Hsieh, D.F.Gibson, and J.F.Tait (2004).
Essential role of B-helix calcium binding sites in annexin V-membrane binding.
  J Biol Chem, 279, 40351-40357.  
12756261 J.M.Isas, D.R.Patel, C.Jao, S.Jayasinghe, J.P.Cartailler, H.T.Haigler, and R.Langen (2003).
Global structural changes in annexin 12. The roles of phospholipid, Ca2+, and pH.
  J Biol Chem, 278, 30227-30234.  
12645006 O.V.Moroz, G.G.Dodson, K.S.Wilson, E.Lukanidin, and I.B.Bronstein (2003).
Multiple structural states of S100A12: A key to its functional diversity.
  Microsc Res Tech, 60, 581-592.  
14611318 T.Risse, W.L.Hubbell, J.M.Isas, and H.T.Haigler (2003).
Structure and dynamics of annexin 12 bound to a planar lipid bilayer.
  Phys Rev Lett, 91, 188101.  
11814339 J.M.Isas, R.Langen, H.T.Haigler, and W.L.Hubbell (2002).
Structure and dynamics of a helical hairpin and loop region in annexin 12: a site-directed spin labeling study.
  Biochemistry, 41, 1464-1473.  
12146973 K.Kastl, M.Ross, V.Gerke, and C.Steinem (2002).
Kinetics and thermodynamics of annexin A1 binding to solid-supported membranes: a QCM study.
  Biochemistry, 41, 10087-10094.  
12069788 L.Columbus, and W.L.Hubbell (2002).
A new spin on protein dynamics.
  Trends Biochem Sci, 27, 288-295.  
12199706 L.Liu, E.Enright, P.Sun, S.Y.Tsai, P.Mehta, D.L.Beckman, and D.M.Terrian (2002).
Inactivation of annexin II tetramer by S-nitrosoglutathione.
  Eur J Biochem, 269, 4277-4286.  
11856825 O.V.Moroz, A.A.Antson, E.J.Dodson, H.J.Burrell, S.J.Grist, R.M.Lloyd, N.J.Maitland, G.G.Dodson, K.S.Wilson, E.Lukanidin, and I.B.Bronstein (2002).
The structure of S100A12 in a hexameric form and its proposed role in receptor signalling.
  Acta Crystallogr D Biol Crystallogr, 58, 407-413.
PDB code: 1gqm
10715122 J.M.Isas, J.P.Cartailler, Y.Sokolov, D.R.Patel, R.Langen, H.Luecke, J.E.Hall, and H.T.Haigler (2000).
Annexins V and XII insert into bilayers at mildly acidic pH and form ion channels.
  Biochemistry, 39, 3015-3022.  
10704197 J.P.Cartailler, H.T.Haigler, and H.Luecke (2000).
Annexin XII E105K crystal structure: identification of a pH-dependent switch for mutant hexamerization.
  Biochemistry, 39, 2475-2483.
PDB code: 1dm5
11087353 J.Sopkova-De Oliveira Santos, S.Fischer, C.Guilbert, A.Lewit-Bentley, and J.C.Smith (2000).
Pathway for large-scale conformational change in annexin V.
  Biochemistry, 39, 14065-14074.  
10951188 P.M.Jones, and A.M.George (2000).
Symmetry and structure in P-glycoprotein and ABC transporters what goes around comes around.
  Eur J Biochem, 267, 5298-5305.  
  10779315 Y.Sokolov, W.S.Mailliard, N.Tranngo, M.Isas, H.Luecke, H.T.Haigler, and J.E.Hall (2000).
Annexins V and XII alter the properties of planar lipid bilayers seen by conductance probes.
  J Gen Physiol, 115, 571-582.  
10353474 F.Russo-Marie (1999).
Annexin V and phospholipid metabolism.
  Clin Chem Lab Med, 37, 287-291.  
10220332 J.Sopkova, M.Vincent, M.Takahashi, A.Lewit-Bentley, and J.Gallay (1999).
Conformational flexibility of domain III of annexin V at membrane/water interfaces.
  Biochemistry, 38, 5447-5458.  
9711292 A.Szewczyk, and S.PikuĊ‚a (1998).
Adenosine 5'-triphosphate: an intracellular metabolic messenger.
  Biochim Biophys Acta, 1365, 333-353.  
  9834142 C.Li, S.Breton, R.Morrison, C.L.Cannon, F.Emma, R.Sanchez-Olea, C.Bear, and K.Strange (1998).
Recombinant pICln forms highly cation-selective channels when reconstituted into artificial and biological membranes.
  J Gen Physiol, 112, 727-736.  
9744874 F.Lafont, S.Lecat, P.Verkade, and K.Simons (1998).
Annexin XIIIb associates with lipid microdomains to function in apical delivery.
  J Cell Biol, 142, 1413-1427.  
9477969 O.Saurel, L.Cézanne, A.Milon, J.F.Tocanne, and P.Demange (1998).
Influence of annexin V on the structure and dynamics of phosphatidylcholine/phosphatidylserine bilayers: a fluorescence and NMR study.
  Biochemistry, 37, 1403-1410.  
9712869 R.Langen, J.M.Isas, H.Luecke, H.T.Haigler, and W.L.Hubbell (1998).
Membrane-mediated assembly of annexins studied by site-directed spin labeling.
  J Biol Chem, 273, 22453-22457.  
9826653 R.Langen, J.M.Isas, W.L.Hubbell, and H.T.Haigler (1998).
A transmembrane form of annexin XII detected by site-directed spin labeling.
  Proc Natl Acad Sci U S A, 95, 14060-14065.  
9497364 T.Sudo, and H.Hidaka (1998).
Regulation of calcyclin (S100A6) binding by alternative splicing in the N-terminal regulatory domain of annexin XI isoforms.
  J Biol Chem, 273, 6351-6357.  
9818271 W.L.Hubbell, A.Gross, R.Langen, and M.A.Lietzow (1998).
Recent advances in site-directed spin labeling of proteins.
  Curr Opin Struct Biol, 8, 649-656.  
9182528 G.Kassam, A.Manro, C.E.Braat, P.Louie, S.L.Fitzpatrick, and D.M.Waisman (1997).
Characterization of the heparin binding properties of annexin II tetramer.
  J Biol Chem, 272, 15093-15100.  
9047302 H.M.Kang, G.Kassam, S.E.Jarvis, S.L.Fitzpatrick, and D.M.Waisman (1997).
Characterization of human recombinant annexin II tetramer purified from bacteria: role of N-terminal acetylation.
  Biochemistry, 36, 2041-2050.  
9099718 M.F.Rosenberg, R.Callaghan, R.C.Ford, and C.F.Higgins (1997).
Structure of the multidrug resistance P-glycoprotein to 2.5 nm resolution determined by electron microscopy and image analysis.
  J Biol Chem, 272, 10685-10694.  
  17708913 S.E.Moss (1997).
  Trends Cell Biol, 7, 87-89.  
9116015 T.Kirsch, H.D.Nah, D.R.Demuth, G.Harrison, E.E.Golub, S.L.Adams, and M.Pacifici (1997).
Annexin V-mediated calcium flux across membranes is dependent on the lipid composition: implications for cartilage mineralization.
  Biochemistry, 36, 3359-3367.  
9166414 T.Kirsch, H.D.Nah, I.M.Shapiro, and M.Pacifici (1997).
Regulated production of mineralization-competent matrix vesicles in hypertrophic chondrocytes.
  J Cell Biol, 137, 1149-1160.  
9223619 V.Gerke, and S.E.Moss (1997).
Annexins and membrane dynamics.
  Biochim Biophys Acta, 1357, 129-154.  
  9165062 W.Baumeister, Z.Cejka, M.Kania, and E.Seemüller (1997).
The proteasome: a macromolecular assembly designed to confine proteolysis to a nanocompartment.
  Biol Chem, 378, 121-130.  
9220993 W.S.Mailliard, H.Luecke, and H.T.Haigler (1997).
Annexin XII forms calcium-dependent multimers in solution and on phospholipid bilayers: a chemical cross-linking study.
  Biochemistry, 36, 9045-9050.  
8706680 M.T.Alvarez-Martinez, J.C.Mani, F.Porte, C.Faivre-Sarrailh, J.P.Liautard, and J.Sri Widada (1996).
Characterization of the interaction between annexin I and profilin.
  Eur J Biochem, 238, 777-784.  
  18475732 P.H.Voermans, K.G.Go, G.J.Horst, M.H.Ruiters, E.Solito, and L.Parente (1996).
Induction of annexin-1 at transcriptional and post-transcriptional level in rat brain by methylprednisolone and the 21-aminosteroid U74389F.
  Mediators Inflamm, 5, 370-378.  
8710873 S.Karlin, and Z.Y.Zhu (1996).
Characterizations of diverse residue clusters in protein three-dimensional structures.
  Proc Natl Acad Sci U S A, 93, 8344-8349.  
8898867 T.Dubois, J.P.Oudinet, J.P.Mira, and F.Russo-Marie (1996).
Annexins and protein kinases C.
  Biochim Biophys Acta, 1313, 290-294.  
8710874 Z.Y.Zhu, and S.Karlin (1996).
Clusters of charged residues in protein three-dimensional structures.
  Proc Natl Acad Sci U S A, 93, 8350-8355.  
7477399 S.E.Moss (1995).
Ion channels. Annexins taken to task.
  Nature, 378, 446-447.  
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.