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PDBsum entry 1avr

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protein ligands metals links
Calcium/phospholipid binding PDB id
1avr
Jmol
Contents
Protein chain
317 a.a. *
Ligands
SO4 ×2
Metals
_CA ×5
Waters ×202
* Residue conservation analysis
PDB id:
1avr
Name: Calcium/phospholipid binding
Title: Crystal and molecular structure of human annexin v after refinement. Implications for structure, membrane binding and ion channel formation of the annexin family of proteins
Structure: Annexin v. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
2.30Å     R-factor:   0.184    
Authors: R.Huber,R.Berendes,A.Burger,M.Schneider,A.Karshikov, H.Luecke,J.Roemisch,E.Paques
Key ref:
R.Huber et al. (1992). Crystal and molecular structure of human annexin V after refinement. Implications for structure, membrane binding and ion channel formation of the annexin family of proteins. J Mol Biol, 223, 683-704. PubMed id: 1311770 DOI: 10.1016/0022-2836(92)90984-R
Date:
17-Oct-91     Release date:   31-Jan-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P08758  (ANXA5_HUMAN) -  Annexin A5
Seq:
Struc:
320 a.a.
317 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     endothelial microparticle   6 terms 
  Biological process     response to organic substance   7 terms 
  Biochemical function     phospholipid binding     4 terms  

 

 
DOI no: 10.1016/0022-2836(92)90984-R J Mol Biol 223:683-704 (1992)
PubMed id: 1311770  
 
 
Crystal and molecular structure of human annexin V after refinement. Implications for structure, membrane binding and ion channel formation of the annexin family of proteins.
R.Huber, R.Berendes, A.Burger, M.Schneider, A.Karshikov, H.Luecke, J.Römisch, E.Paques.
 
  ABSTRACT  
 
Two crystal forms (P6(3) and R3) of human annexin V have been crystallographically refined at 2.3 A and 2.0 A resolution to R-values of 0.184 and 0.174, respectively, applying very tight stereochemical restraints with deviations from ideal geometry of 0.01 A and 2 degrees. The three independent molecules (2 in P6(3), 1 in R3) are similar, with deviations in C alpha positions of 0.6 A. The polypeptide chain of 320 amino acid residues is folded into a planar cyclic arrangement of four repeats. The repeats have similar structures of five alpha-helical segments wound into a right-handed compact superhelix. Three calcium ion sites in repeats I, II and IV and two lanthanum ion sites in repeat I have been found in the R3 crystals. They are located at the convex face of the molecule opposite the N terminus. Repeat III has a different conformation at this site and no calcium bound. The calcium sites are similar to the phospholipase A2 calcium-binding site, suggesting analogy also in phospholipid interaction. The center of the molecule is formed by a channel of polar charged residues, which also harbors a chain of ordered water molecules conserved in the different crystal forms. Comparison with amino acid sequences of other annexins shows a high degree of similarity between them. Long insertions are found only at the N termini. Most conserved are the residues forming the metal-binding sites and the polar channel. Annexins V and VII form voltage-gated calcium ion channels when bound to membranes in vitro. We suggest that annexins bind with their convex face to membranes, causing local disorder and permeability of the phospholipid bilayers. Annexins are Janus-faced proteins that face phospholipid and water and mediate calcium transport.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. uperposition of he alcium inding site f phospholipase A, with site Cal of nnexin V. ----. phospholipase A,; e, annexin.
Figure 7.
IIE
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1992, 223, 683-704) copyright 1992.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21468022 A.Bouter, C.Gounou, R.Bérat, S.Tan, B.Gallois, T.Granier, B.L.d'Estaintot, E.Pöschl, B.Brachvogel, and A.R.Brisson (2011).
Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair.
  Nat Commun, 2, 270.
PDB code: 2h0k
18795951 A.C.Rintala-Dempsey, A.Rezvanpour, and G.S.Shaw (2008).
S100-annexin complexes--structural insights.
  FEBS J, 275, 4956-4966.  
18174168 B.Jeppesen, C.Smith, D.F.Gibson, and J.F.Tait (2008).
Entropic and enthalpic contributions to annexin V-membrane binding: a comprehensive quantitative model.
  J Biol Chem, 283, 6126-6135.  
18441010 N.J.Hu, A.M.Yusof, A.Winter, A.Osman, A.K.Reeve, and A.Hofmann (2008).
The crystal structure of calcium-bound annexin Gh1 from Gossypium hirsutum and its implications for membrane binding mechanisms of plant annexins.
  J Biol Chem, 283, 18314-18322.
PDB code: 3brx
17993484 N.J.Hu, J.Bradshaw, H.Lauter, J.Buckingham, E.Solito, and A.Hofmann (2008).
Membrane-induced folding and structure of membrane-bound annexin A1 N-terminal peptides: implications for annexin-induced membrane aggregation.
  Biophys J, 94, 1773-1781.  
17613532 B.R.Genge, L.N.Wu, and R.E.Wuthier (2007).
In vitro modeling of matrix vesicle nucleation: synergistic stimulation of mineral formation by annexin A5 and phosphatidylserine.
  J Biol Chem, 282, 26035-26045.  
17028130 N.Colloc'h, J.Sopkova-de Oliveira Santos, P.Retailleau, D.Vivarès, F.Bonneté, B.Langlois d'Estainto, B.Gallois, A.Brisson, J.J.Risso, M.Lemaire, T.Prangé, and J.H.Abraini (2007).
Protein crystallography under xenon and nitrous oxide pressure: comparison with in vivo pharmacology studies and implications for the mechanism of inhaled anesthetic action.
  Biophys J, 92, 217-224.
PDB codes: 2iba 2ic0 2icq 2ie6 2ie7
17355882 P.Pathuri, E.T.Nguyen, S.G.Svärd, and H.Luecke (2007).
Apo and calcium-bound crystal structures of Alpha-11 giardin, an unusual annexin from Giardia lamblia.
  J Mol Biol, 368, 493-508.
PDB codes: 2ii2 2iic
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.  
17552907 Y.Zhang, K.H.Wang, Y.J.Guo, Y.M.Lu, H.L.Yan, Y.L.Song, F.Wang, F.X.Ding, and S.H.Sun (2007).
Annexin B1 from Taenia solium metacestodes is a newly characterized member of the annexin family.
  Biol Chem, 388, 601-610.  
16419147 F.Merzel, M.Hodoscek, D.Janezic, and A.Sanson (2006).
New force field for calcium binding sites in annexin-membrane complexes.
  J Comput Chem, 27, 446-452.  
  15872355 J.F.Tait, C.Smith, and F.G.Blankenberg (2005).
Structural requirements for in vivo detection of cell death with 99mTc-annexin V.
  J Nucl Med, 46, 807-815.  
15928709 V.Gerke, C.E.Creutz, and S.E.Moss (2005).
Annexins: linking Ca2+ signalling to membrane dynamics.
  Nat Rev Mol Cell Biol, 6, 449-461.  
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.  
12665588 B.Brachvogel, J.Dikschas, H.Moch, H.Welzel, K.von der Mark, C.Hofmann, and E.Pöschl (2003).
Annexin A5 is not essential for skeletal development.
  Mol Cell Biol, 23, 2907-2913.  
12401794 Y.Mo, B.Campos, T.R.Mealy, L.Commodore, J.F.Head, J.R.Dedman, and B.A.Seaton (2003).
Interfacial basic cluster in annexin V couples phospholipid binding and trimer formation on membrane surfaces.
  J Biol Chem, 278, 2437-2443.
PDB codes: 1n41 1n42 1n44
12142457 A.Hofmann, S.Ruvinov, S.Hess, R.Schantz, D.P.Delmer, and A.Wlodawer (2002).
Plant annexins form calcium-independent oligomers in solution.
  Protein Sci, 11, 2033-2040.  
11910038 F.Ochsenbein, J.M.Neumann, E.Guittet, and C.van Heijenoort (2002).
Dynamical characterization of residual and non-native structures in a partially folded protein by (15)N NMR relaxation using a model based on a distribution of correlation times.
  Protein Sci, 11, 957-964.  
12070314 J.Sopkova, C.Raguenes-Nicol, M.Vincent, A.Chevalier, A.Lewit-Bentley, F.Russo-Marie, and J.Gallay (2002).
Ca(2+) and membrane binding to annexin 3 modulate the structure and dynamics of its N terminus and domain III.
  Protein Sci, 11, 1613-1625.  
12324445 J.Turnay, N.Olmo, M.Gasset, I.Iloro, J.L.Arrondo, and M.A.Lizarbe (2002).
Calcium-dependent conformational rearrangements and protein stability in chicken annexin A5.
  Biophys J, 83, 2280-2291.  
12124256 T.Huynh, J.C.Smith, and A.Sanson (2002).
Protein unfolding transitions in an intrinsically unstable annexin domain: molecular dynamics simulation and comparison with nuclear magnetic resonance data.
  Biophys J, 83, 681-698.  
  11696990 L.Jennings, L.Wu, K.B.King, H.Hämmerle, G.Cs-Szabo, and J.Mollenhauer (2001).
The effects of collagen fragments on the extracellular matrix metabolism of bovine and human chondrocytes.
  Connect Tissue Res, 42, 71-86.  
11781014 M.S.Kurtis, B.P.Tu, O.A.Gaya, J.Mollenhauer, W.Knudson, R.F.Loeser, C.B.Knudson, and R.L.Sah (2001).
Mechanisms of chondrocyte adhesion to cartilage: role of beta1-integrins, CD44, and annexin V.
  J Orthop Res, 19, 1122-1130.  
10634937 A.G.Buckland, and D.C.Wilton (2000).
Anionic phospholipids, interfacial binding and the regulation of cell functions.
  Biochim Biophys Acta, 1483, 199-216.  
10869176 A.Hofmann, C.Raguénès-Nicol, B.Favier-Perron, J.Mesonero, R.Huber, F.Russo-Marie, and A.Lewit-Bentley (2000).
The annexin A3-membrane interaction is modulated by an N-terminal tryptophan.
  Biochemistry, 39, 7712-7721.  
11106498 J.Ayala-Sanmartin, P.Gouache, and J.P.Henry (2000).
N-Terminal domain of annexin 2 regulates Ca(2+)-dependent membrane aggregation by the core domain: a site directed mutagenesis study.
  Biochemistry, 39, 15190-15198.  
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.  
  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.  
10052949 L.Cézanne, A.Lopez, F.Loste, G.Parnaud, O.Saurel, P.Demange, and J.F.Tocanne (1999).
Organization and dynamics of the proteolipid complexes formed by annexin V and lipids in planar supported lipid bilayers.
  Biochemistry, 38, 2779-2786.  
9890889 L.Silvestro, and P.H.Axelsen (1999).
Fourier transform infrared linked analysis of conformational changes in annexin V upon membrane binding.
  Biochemistry, 38, 113-121.  
10450084 S.Hayward (1999).
Structural principles governing domain motions in proteins.
  Proteins, 36, 425-435.  
9446599 A.Hofmann, A.Escherich, A.Lewit-Bentley, J.Benz, C.Raguenes-Nicol, F.Russo-Marie, V.Gerke, L.Moroder, and R.Huber (1998).
Interactions of benzodiazepine derivatives with annexins.
  J Biol Chem, 273, 2885-2894.  
9609693 B.Campos, Y.D.Mo, T.R.Mealy, C.W.Li, M.A.Swairjo, C.Balch, J.F.Head, G.Retzinger, J.R.Dedman, and B.A.Seaton (1998).
Mutational and crystallographic analyses of interfacial residues in annexin V suggest direct interactions with phospholipid membrane components.
  Biochemistry, 37, 8004-8010.
PDB codes: 1bc0 1bc1 1bc3 1bcw 1bcy 1bcz
9671526 F.M.Megli, M.Selvaggi, S.Liemann, E.Quagliariello, and R.Huber (1998).
The calcium-dependent binding of annexin V to phospholipid vesicles influences the bilayer inner fluidity gradient.
  Biochemistry, 37, 10540-10546.  
9721677 I.Kovács, F.Ayaydin, A.Oberschall, I.Ipacs, S.Bottka, S.Pongor, D.Dudits, and E.C.Tóth (1998).
Immunolocalization of a novel annexin-like protein encoded by a stress and abscisic acid responsive gene in alfalfa.
  Plant J, 15, 185-197.  
9718321 J.Sopkova, M.Vincent, M.Takahashi, A.Lewit-Bentley, and J.Gallay (1998).
Conformational flexibility of domain III of annexin V studied by fluorescence of tryptophan 187 and circular dichroism: the effect of pH.
  Biochemistry, 37, 11962-11970.  
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.  
9111038 B.Perron, A.Lewit-Bentley, B.Geny, and F.Russo-Marie (1997).
Can enzymatic activity, or otherwise, be inferred from structural studies of annexin III?
  J Biol Chem, 272, 11321-11326.
PDB code: 1aii
9013554 C.Bellagamba, I.Hubaishy, J.D.Bjorge, S.L.Fitzpatrick, D.J.Fujita, and D.M.Waisman (1997).
Tyrosine phosphorylation of annexin II tetramer is stimulated by membrane binding.
  J Biol Chem, 272, 3195-3199.  
9099690 J.P.Mira, T.Dubois, J.P.Oudinet, S.Lukowski, F.Russo-Marie, and B.Geny (1997).
Inhibition of cytosolic phospholipase A2 by annexin V in differentiated permeabilized HL-60 cells. Evidence of crucial importance of domain I type II Ca2+-binding site in the mechanism of inhibition.
  J Biol Chem, 272, 10474-10482.  
9186609 K.A.Hajjar, and J.S.Menell (1997).
Annexin II: a novel mediator of cell surface plasmin generation.
  Ann N Y Acad Sci, 811, 337-349.  
9048549 T.Vogl, C.Jatzke, H.J.Hinz, J.Benz, and R.Huber (1997).
Thermodynamic stability of annexin V E17G: equilibrium parameters from an irreversible unfolding reaction.
  Biochemistry, 36, 1657-1668.  
  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.  
8639653 B.Favier-Perron, A.Lewit-Bentley, and F.Russo-Marie (1996).
The high-resolution crystal structure of human annexin III shows subtle differences with annexin V.
  Biochemistry, 35, 1740-1744.
PDB code: 1axn
8756690 F.Cordier-Ochsenbein, R.Guerois, F.Baleux, T.Huynh-Dinh, A.Chaffotte, J.M.Neumann, and A.Sanson (1996).
Folding properties of an annexin I domain: a 1H-15N NMR and CD study.
  Biochemistry, 35, 10347-10357.  
8727316 F.Zhou, and K.Schulten (1996).
Molecular dynamics study of phospholipase A2 on a membrane surface.
  Proteins, 25, 12-27.  
8725344 J.M.Naciff, M.A.Kaetzel, M.M.Behbehani, and J.R.Dedman (1996).
Differential expression of annexins I-VI in the rat dorsal root ganglia and spinal cord.
  J Comp Neurol, 368, 356-370.  
8702954 K.A.Hajjar, C.A.Guevara, E.Lev, K.Dowling, and J.Chacko (1996).
Interaction of the fibrinolytic receptor, annexin II, with the endothelial cell surface. Essential role of endonexin repeat 2.
  J Biol Chem, 271, 21652-21659.  
9072184 M.Knochel, R.Kissmehl, J.D.Wissmann, M.Momayezi, J.Hentschel, H.Plattner, and R.D.Burgoyne (1996).
Annexins in Paramecium cells. Involvement in site-specific positioning of secretory organelles.
  Histochem Cell Biol, 105, 269-281.  
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.  
8682860 S.Chasserot-Golaz, N.Vitale, I.Sagot, B.Delouche, S.Dirrig, L.A.Pradel, J.P.Henry, D.Aunis, and M.F.Bader (1996).
Annexin II in exocytosis: catecholamine secretion requires the translocation of p36 to the subplasmalemmal region in chromaffin cells.
  J Cell Biol, 133, 1217-1236.  
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.  
8569730 B.J.Nichols, and R.M.Denton (1995).
Towards the molecular basis for the regulation of mitochondrial dehydrogenases by calcium ions.
  Mol Cell Biochem, 149, 203-212.  
8569746 D.M.Waisman (1995).
Annexin II tetramer: structure and function.
  Mol Cell Biochem, 149, 301-322.  
7477411 H.Luecke, B.T.Chang, W.S.Mailliard, D.D.Schlaepfer, and H.T.Haigler (1995).
Crystal structure of the annexin XII hexamer and implications for bilayer insertion.
  Nature, 378, 512-515.
PDB code: 1aei
7665573 J.F.Tait, S.Engelhardt, C.Smith, and K.Fujikawa (1995).
Prourokinase-annexin V chimeras. Construction, expression, and characterization of recombinant proteins.
  J Biol Chem, 270, 21594-21599.  
7607253 N.Budisa, B.Steipe, P.Demange, C.Eckerskorn, J.Kellermann, and R.Huber (1995).
High-level biosynthetic substitution of methionine in proteins by its analogs 2-aminohexanoic acid, selenomethionine, telluromethionine and ethionine in Escherichia coli.
  Eur J Biochem, 230, 788-796.  
7788288 S.Liemann, and A.Lewit-Bentley (1995).
Annexins: a novel family of calcium- and membrane-binding proteins in search of a function.
  Structure, 3, 233-237.  
7816934 C.K.Damer, and C.E.Creutz (1994).
Secretory and synaptic vesicle membrane proteins and their possible roles in regulated exocytosis.
  Prog Neurobiol, 43, 511-536.  
8055967 H.Nakao, M.Watanabe, and M.Maki (1994).
A new function of calphobindin I (annexin V). Promotion of both migration and urokinase-type plasminogen activator activity of normal human keratinocytes.
  Eur J Biochem, 223, 901-908.  
7957219 J.M.Neumann, A.Sanson, and A.Lewit-Bentley (1994).
Calcium-induced changes in annexin V behaviour in solution as seen by proton NMR spectroscopy.
  Eur J Biochem, 225, 819-825.  
8056721 N.Kaneko, R.Matsuda, F.Chiwaki, and S.Hosoda (1994).
Purification of cardiac annexin V from the beagle dog heart and changes in its localization in the ischemic rat heart.
  Heart Vessels, 9, 148-154.  
7519374 P.Demange, D.Voges, J.Benz, S.Liemann, P.Göttig, R.Berendes, A.Burger, and R.Huber (1994).
Annexin V: the key to understanding ion selectivity and voltage regulation?
  Trends Biochem Sci, 19, 272-276.  
8154759 R.D.Burgoyne, A.Morgan, and D.Roth (1994).
Characterization of proteins that regulate calcium-dependent exocytosis in adrenal chromaffin cells.
  Ann N Y Acad Sci, 710, 333-346.  
8073497 R.D.Burgoyne, and M.J.Clague (1994).
Annexins in the endocytic pathway.
  Trends Biochem Sci, 19, 231-232.  
1446685 A.Lewit-Bentley, S.Morera, R.Huber, and G.Bodo (1992).
The effect of metal binding on the structure of annexin V and implications for membrane binding.
  Eur J Biochem, 210, 73-77.
PDB code: 1anw
1381122 C.W.Heizmann, and K.Braun (1992).
Changes in Ca(2+)-binding proteins in human neurodegenerative disorders.
  Trends Neurosci, 15, 259-264.  
1386288 H.C.Lin, T.C.Südhof, and R.G.Anderson (1992).
Annexin VI is required for budding of clathrin-coated pits.
  Cell, 70, 283-291.  
15336007 P.Freemont, R.Newman, and H.Driessen (1992).
Janus-faced proteins.
  Curr Biol, 2, 98.  
1423614 T.N.Davis (1992).
What's new with calcium?
  Cell, 71, 557-564.  
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.