|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0002198,
umls-concept:C0003250,
umls-concept:C0023621,
umls-concept:C0086418,
umls-concept:C0220908,
umls-concept:C0242831,
umls-concept:C0439851,
umls-concept:C0597358,
umls-concept:C1514562,
umls-concept:C1519025,
umls-concept:C1552596,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221,
umls-concept:C1947931
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
1997-12-8
|
|
pubmed:abstractText |
The human proteinase inhibitor, alpha2-macroglobulin (a2-M), inhibits a large number of proteinases. Alpha2-M-proteinase complexes are rapidly cleared from the circulation by binding to a cellular receptor (alpha2-M-R/LRP) via the receptor binding domain (RBD) which is made up of a 20 kDa C-terminal stretch of the 180 kDa monomer of the inhibitor. A monoclonal antibody (mab alpha-1) has been described which reacts with the receptor-recognizable form of the inhibitor, the so called transformed alpha2-M (a2-Mt). By screening of a phage display library an epitope in the RBD of the inhibitor was identified that reacts with mab alpha-1. Out of 25 phage clones a heptapeptide sequence (S-x1-x2-D-x3-x4-K) was obtained containing identical amino acids in three positions. A consensus peptide (S-R-S-D-P-P-K) was synthesized and found to displace alpha2-Mt from binding to mab alpha-1 and to receptor. The specificity of competition was demonstrated by a reversed peptide and a control antibody. By structural comparison it was found that the consensus heptapeptide mimics a discontinuous conformationally constrained epitope present in the RBD of the inhibitor. This is the first report describing the detection of discontinuous epitopes by phage display using a short linear peptide.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Oct
|
|
pubmed:issn |
0014-5793
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
20
|
|
pubmed:volume |
416
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
193-6
|
|
pubmed:dateRevised |
2011-11-17
|
|
pubmed:meshHeading |
pubmed-meshheading:9369213-Amino Acid Sequence,
pubmed-meshheading:9369213-Animals,
pubmed-meshheading:9369213-Antibodies, Monoclonal,
pubmed-meshheading:9369213-Binding, Competitive,
pubmed-meshheading:9369213-Binding Sites,
pubmed-meshheading:9369213-Cattle,
pubmed-meshheading:9369213-Epitopes,
pubmed-meshheading:9369213-Humans,
pubmed-meshheading:9369213-Kinetics,
pubmed-meshheading:9369213-Low Density Lipoprotein Receptor-Related Protein-1,
pubmed-meshheading:9369213-Models, Structural,
pubmed-meshheading:9369213-Molecular Sequence Data,
pubmed-meshheading:9369213-Molecular Weight,
pubmed-meshheading:9369213-Peptide Library,
pubmed-meshheading:9369213-Protein Conformation,
pubmed-meshheading:9369213-Receptors, Immunologic,
pubmed-meshheading:9369213-Sequence Alignment,
pubmed-meshheading:9369213-Sequence Homology, Amino Acid,
pubmed-meshheading:9369213-alpha-Macroglobulins
|
|
pubmed:year |
1997
|
|
pubmed:articleTitle |
Epitope mapping by screening of phage display libraries of a monoclonal antibody directed against the receptor binding domain of human alpha2-macroglobulin.
|
|
pubmed:affiliation |
Institute of Biochemistry, Medical Faculty, University of Leipzig, Germany. birg@medizin.uni-leipzig.de
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
