Linked Life Data

1387643

Source:http://linkedlifedata.com/resource/pubmed/id/1387643

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
1992-10-7
pubmed:abstractText
In 1985 we isolated a new vascular anticoagulant protein VAC alpha, now called annexin V, with a high binding affinity (Kd less than 10(-10) M) for phospholipids. Its anticoagulant effect was attributed to displacement of coagulation factors from the phospholipid membrane. The present study demonstrates that the inhibition of prothrombinase activity by annexin V strongly depends on the curvature of the membrane surface and on the calcium concentration. Half-maximal inhibition of prothrombinase on and binding of annexin V to small vesicles, composed of 20% phosphatidylserine and 80% phosphatidylcholine, requires 2-3 mM calcium. With large vesicles and planar bilayers considerably less calcium is required for inhibition of prothrombinase and for lipid binding. Half-maximal binding of annexin V to large vesicles and to planar bilayers occurs at 0.7 and 0.2 mM calcium, respectively. This seemingly confirms the displacement model. The displacement of coagulation factors, however, proved to be incomplete, with residual surface concentrations of factors Xa, Va, and prothrombin sufficient for effective production of thrombin. Cryoelectron microscopy revealed that annexin V binding to large vesicles caused planar facets, indicating the formation of large sheets of clustered annexin V. Apparently, the formation of these two-dimensional arrays is promoted by calcium and hampered by high surface curvature. It is speculated that the complete inhibition (greater than 99%) of prothrombinase activity by annexin V is caused by the reduced lateral mobility of prothrombin and factor Xa in rigid sheets of annexin V covering the membrane.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Annexin A5, http://linkedlifedata.com/resource/pubmed/chemical/Anticoagulants, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Factor Xa, http://linkedlifedata.com/resource/pubmed/chemical/Lipid Bilayers, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylcholines, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylserines, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipids, http://linkedlifedata.com/resource/pubmed/chemical/Pregnancy Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Thromboplastin
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
267
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17907-12
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Clustering of lipid-bound annexin V may explain its anticoagulant effect.
pubmed:affiliation
Cardiovascular Research Institute Maastricht, University of Limburg, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't