Linked Life Data

7540175

Source:http://linkedlifedata.com/resource/pubmed/id/7540175

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
1995-7-17
pubmed:abstractText
High and low molecular mass kininogen, two multidomain plasma proteins, bind to endothelial cells, platelets, and neutrophils in the intravascular compartment. The specific cell attachment site on their common heavy chain is mediated by domain-3, a cystatin-like structure with inhibitory capacity for papain-like proteinases (Jiang, Y., Müller-Esterl, W., and Schmaier, A. H. (1992) J. Biol. Chem. 267, 3712-3717). In this report, the domain-3 cell binding site is determined by an antibody-directed strategy. The epitope of monoclonal antibody HKH15, which binds to domain-3 and blocks the binding of kininogens to platelets and endothelial cells, was mapped using seven synthetic peptides, which span the entire domain-3 sequence. One peptide, LDC27, specifically bound to HKH15. Fine mapping of the epitope of HKH15 revealed that a minimal 13-residue segment in LDC27, named CNA13, is the antibody binding site. LDC27 and CNA13 inhibited biotinylated high molecular mass kininogen binding to endothelial cells with apparent IC50 values of 60.3 +/- 12 and 113.3 +/- 63.7 microM, respectively. Carboxymethylated papain and affinity-purified anti-LDC27 polyclonal antibodies also inhibited the binding of biotinylated high molecular mass kininogen to endothelial cells with an apparent IC50 of 1.04 microM and 59 nM, respectively. Biotinylated LDC27 itself directly bound to endothelial cells, and domain-3 inhibited biotinylated LDC27 binding to human umbilical vein endothelial cells with an IC50 of 41 nM. Using the crystalline structure of cystatin to computer model domain-3, LDC27 and CNA13 were located in the second hairpin loop of the reactive site of cystatin-like proteins (Bode, W., Engh, R., Musil, D., Thiele, U. Huber, R., Karshikov, A., Brzin, J., Kos, J., and Turk, V. (1988) EMBO J. 7, 2593-2599). These results indicate that the major endothelial cell attachment site on kininogen domain-3 is located on its carboxyl-terminal portion and that it overlaps its cysteine protease inhibitory region.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14634-42
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Identification of an endothelial cell binding site on kininogen domain D3.
pubmed:affiliation
Institute of Physiological Chemistry and Pathobiochemistry, Johannes Gutenberg University, Mainz, Federal Republic of Germany.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't