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Query: UNIPROT:P08758 (annexin V)
 9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID: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. 131 70

Annexins constitute a family of cytosolic, water soluble proteins, which bind to negatively charged phospholipids in a calcium-dependent manner. They display structural and functional features of both soluble and integral membrane proteins. The annexins face the hydrophilic as well as the hydrophobic phase (Janus-faced proteins) and mediate ion transport in vitro. We present the refined structure and molecular model of annexin V at 2.0 A resolution. The molecule is almost entirely alpha-helical, and each of the four repeats of annexin V is folded into a compact domain of similar structure. The four domains are arranged in an almost planar, cyclic array. In the center of the molecule, one can find a prominent hydrophilic pore, which we associate with the calcium-selective channel found in annexin V. Annexin V has an overall flat, slightly curved shape with two faces, one convex and one concave. The three calcium binding sites Ca1 to Ca3, all located at the convex face of the molecule, are assumed to be phospholipid binding sites, as suggested by their structural similarity to the calcium site of phospholipase A2. Soluble and membrane-bound annexin have closely similar structures, as shown by electron microscopic analysis. Several other observations provide evidence that the membrane-anchoring region of the annexin V molecule is located on the convex face. In the last part of this article, the electrophysiology of the annexins is described. Ion permeation occurs in discrete conductance states and is regulated by voltage across the membrane. A model for the annexin V-membrane interaction, the ion channel formation, and the ion conduction pathway is proposed.
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PMID:Annexin V-crystal structure and its implications on function. 138 18

Annexin V is a member of the calcium- and phospholipid-binding proteins, known to have an antithrombotic effect. For the first time, we have tested its ability to prevent intraocular postoperative fibrin formation in a standardised rabbit model and compared its effect with that of heparin. Annexin V, 20 micrograms and 60 micrograms, injected in the anterior chamber post-operatively, significantly reduced the area of the fibrin clot and its time to clearing. Annexin V appeared to be as efficient as heparin. It probably acts by preventing phospholipids from playing their role in the coagulation cascade which leads to fibrin formation. Furthermore, annexin V has an anti-inflammatory effect by protecting phospholipids from phospholipase A2 activity. Therefore, annexin V might be considered as a new therapeutic agent acting both on fibrin formation and inflammatory processes.
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PMID:Inhibition of intraocular fibrin formation with annexin V. 139 May 23

Arachidonic acid is mobilized from fetal membrane phospholipids at parturition leading to increased production of oxytocic prostaglandins which may initiate or maintain myometrial contractions. Phospholipid mobilization requires activation of phospholipase A2 or C, both of which require calcium for activity. The annexins (lipocortins) are a superfamily of proteins which bind to calcium and phospholipids and thereby may alter phospholipase activity through two mechanisms: modulation of intracellular free Ca2+ concentrations or regulation of the accessibility of phospholipids to hydrolyzing enzymes. Using Western immunoblotting with monospecific polyclonal antibodies, annexins I-VI were identified in human amnion and chorion/decidua at term in tissues obtained from patients in labor or not in labor. Each annexin was present in two distinct pools: a pool which only associated with the membrane in the presence of calcium (calcium-dependent pool) and a calcium-independent pool that remained membrane bound in the presence of calcium chelators. Annexin I was present as two species, resolving at 36 kDa and 68 kDa. The total concentration of annexin I in both amnion and chorion/decidua was significantly decreased with labor, while the total concentration of annexin V in chorion significantly increased with labor. The size of individual pools of annexins also changed with labor: the calcium-dependent pool of annexins I and II in both amnion and chorion significantly decreased; the calcium-dependent pool of annexin V increased in chorion; and calcium-independent pools of annexin I in amnion and annexins I, II, and V in chorion significantly decreased with labor. The decrease in total annexin I concentration with labor in amnion reflects a substantial decrease (80-90%) in the pool tightly bound to the membrane in a calcium-independent manner. This striking change distinguishes annexin I as a potential candidate inhibitor which is specifically downregulated at parturition, potentially leading to increased access of phospholipases to substrate phospholipids and increased prostaglandin production at labor.
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PMID:Changes in annexin (lipocortin) content in human amnion and chorion at parturition. 146 69

Distinct peptide maps of two rabbit lung Ca2(+)-dependent phospholipid-binding proteins (PLBPs), 36,000 and 33,000, were generated by cyanogen bromide (CNBr) cleavage, trypsin or Staphylococcus aureus V8 proteinase digestion. The amino acid sequence of a CNBr-cleaved peptide of the 36,000 PLBP was aligned to the amino terminus of human lipocortin I with more than 77% identity, but had no identity with the known amino terminal sequence of other known annexins. Partial amino acid sequence of a 33,000 PLBP peptide demonstrated a close (56%) relationship to endonexin II, human placental anticoagulant protein, and porcine intestine protein II, but shared only 32% identity with lipocortin I, 30% with lipocortin II. Antiserum generated against purified 36,000 PLBP reacted strongly with the 33,000 PLBP, but did not react with any other rabbit lung cytosolic proteins. Both PLBPs inhibited the phospholipase A2 reaction when dioleoyl phosphatidylcholine and phosphatidylglycerol vesicles or monolayers were used as substrates. In the vesicle assay, the phospholipase A2 reaction was inhibited at lower substrate phospholipid concentrations but not at nearly saturating substrate concentrations. In the monolayer assay, the phospholipid-binding proteins did not inhibit phospholipase A2 at a low phospholipid surface concentration of 3.8.10(-3) molecules/A2, but they did at higher surface concentrations between 1.1 x 10(-2) and 3.8 x 10(-2) molecules/A2. The inhibition of phospholipase A2 by rabbit lung phospholipid-binding proteins is most likely due to the prevention of penetration by phospholipase A2 into the interface, a requirement for the enzyme to act on the substrate.
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PMID:Lung calcium-dependent phospholipid-binding proteins: structure and function. 199 31

Calcimedin is a group of proteins which has a binding ability to several hydrophobic matrices or cellular membrane fractions in the presence of Ca2+. Although the molecular properties were partially clarified, the physiological functions of calcimedins have not been clearly defined. In this study, we describe the isolation and characterization of 32-kDa calcimedin from chicken gizzard. Both structural and functional studies establish that 32-kDa calcimedin is a member of the calpactin/lipocortin family. The 32-kDa calcimedin displays phospholipase A2 inhibitory activity, Ca2(+)-dependent F-actin binding activity, and phospholipid binding activity similar to those of calpactins/lipocortins. Antiendonexin II antibody recognized 32-kDa calcimedin. However, antibodies against calpactin I (lipocortin II), calpactin II (lipocortin I), 35-kDa calcimedin, and 67-kDa calcimedin did not cross-react with 32-kDa calcimedin. One-dimensional peptide maps of the 32-kDa calcimedin and the 35-kDa calcimedin are different, confirming that they are distinct proteins. By comparing the sequence of 32-kDa calcimedin with the predicted sequence of endonexin II, we concluded that the primary structure of the 32-kDa protein is highly conserved. In particular, the sequences AMKGMGTDDEXEIXL, GMGTDEEEIL, VLTEILASR, and ILTSR conform to the endonexin consensus sequence, which is characteristic of the calpactin/lipocortin family.
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PMID:Purification, characterization, and partial sequence analysis of 32-kDa calcimedin from chicken gizzard. 213 84

Two calcium-independent phospholipases isolated from guinea pig pancreas (lipase Ia, 37 kDa) and from guinea pig intestine (phospholipase B, 97 kDa) have been used to probe the mechanism of phospholipase inhibition by lipocortin. In the presence of calcium, both enzymes were inhibited by lipocortin I in a manner very similar to the inhibition of pig pancreas phospholipase A2. By using phospholipases that lack a requirement for calcium, we have for the first time been able to dissociate enzymatic activity from the role of calcium in the inhibitory process. It was found that lipocortin was without effect against phospholipase A1 and phospholipase B in the absence of calcium, under which conditions the inhibitory protein is unable to interact with anionic phospholipid surfaces. The same behavior toward phospholipase A1 was observed with two other related proteins, endonexin II or lipocortin V, and p68/67-kDa calelectrin or lipocortin VI. Together with the observation that lipocortins are active only in the presence of limited amounts of substrate, these data give further support to the "surface depletion model" of lipocortin inhibition, rather than to a mechanism involving a direct interaction between enzyme and inhibitor.
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PMID:Calcium-independent phospholipases from guinea pig digestive tract as probes to study the mechanism of lipocortin. 213 21

EDTA-extractable protein (EEP) is a mixture of major lens membrane proteins with molecular masses ranging from 32 kDa to 40 kDa. These bind to the lens membrane in a Ca2(+)-dependent manner. In the present study we have identified and purified two distinct 32 kDa components of EEP (designated as EEP 32-1 and EEP 32-2) from bovine lens that inhibit phospholipase A2 activity. Both EEP 32-1 and EEP 32-2 bind to phospholipid-containing liposomes and actin filaments in a Ca2(+)-dependent fashion. Immunochemical studies and two-dimensional electrophoreses demonstrate that the two proteins are distinct from one another. Both EEP 32-1 and EEP 32-2 are clearly different from calpactin (lipocortin) or its proteolytic fragments because they did not react with anti-[human placenta calpactin (lipocortin)] antibody. Our results also indicate that EEP 32-1 is very similar to endonexin I and that EEP 32-2 corresponds to endonexin II.
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PMID:Identification of the 32 kDa components of bovine lens EDTA-extractable protein as endonexins I and II. 213 56

Calcium-dependent phospholipid binding and phospholipase A2 inhibitory proteins were isolated from human mononuclear cells. Lipocortins I and II were present whereas lipocortin IV (endonexin I) was not. The other proteins were purified to homogeneity and shown to have molecular masses of 35, 36, 32 and 73 kDa. The 36-kDa and 73-kDa proteins are related, the smaller appears to be part of the larger. The 73-kDa protein is related to the 67-kDa calelectrin and to lipocortin VI; the 32-kDa protein is different from endonexin I but related to chromobindin 7 and to lipocortin V. The 35-kDa protein has been identified by tryptic peptide sequencing as lipocortin III. All these proteins inhibit phospholipase A2 activity in vitro and the three smaller ones inhibit the [3H]arachidonic acid release from prelabelled monocytes induced by the calcium ionophore A23187 in a dose-dependent manner.
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PMID:Identification and characterization of phospholipase A2 inhibitory proteins in human mononuclear cells. 213 36

A cDNA was cloned coding for a new member of the human Ca2+-modulated phospholipid-binding protein family termed annexins. Due to its 56% identity to the human vascular anticoagulant (VAC) the new protein is named VAC-beta, renaming the previous VAC as VAC-alpha. Northern analysis detects one hybridizing mRNA species of 2.2 kb in human placenta. Genomic Southern blot analysis shows a VAC-beta gene of comparable complexity to the VAC-alpha gene. The cDNA was expressed in Escherichia coli and the recombinant protein purified to homogeneity. Antiserum raised against VAC-beta weakly cross-reacts with VAC-alpha. The properties of VAC-beta as an anticoagulant and as an inhibitor of phospholipase A2 activity were analyzed and compared to those of VAC-alpha.
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PMID:Vascular anticoagulant beta: a novel human Ca2+/phospholipid binding protein that inhibits coagulation and phospholipase A2 activity. Its molecular cloning, expression and comparison with VAC-alpha. 253 88


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