Monoclonal antibodies detect receptor-induced binding sites in Glu-plasminogen. 2011

Jaena Han, and Nagyung Baik, and Kee-Hwan Kim, and Jian-Ming Yang, and Gye Won Han, and Yun Gong, and Mercè Jardí, and Francis J Castellino, and Jordi Felez, and Robert J Parmer, and Lindsey A Miles
Departments of Cell Biology, The Scripps Research Institute, La Jolla, CA, USA.

When Glu-plasminogen binds to cells, its activation to plasmin is markedly enhanced compared with the reaction in solution, suggesting that Glu-plasminogen on cell surfaces adopts a conformation distinct from that in solution. However, direct evidence for such conformational changes has not been obtained. Therefore, we developed anti-plasminogen mAbs to test the hypothesis that Glu-plasminogen undergoes conformational changes on its interaction with cells. Six anti-plasminogen mAbs (recognizing 3 distinct epitopes) that preferentially recognized receptor-induced binding sites (RIBS) in Glu-plasminogen were obtained. The mAbs also preferentially recognized Glu-plasminogen bound to the C-terminal peptide of the plasminogen receptor, Plg-R(KT), and to fibrin, plasmin-treated fibrinogen, and Matrigel. We used trypsin proteolysis, immunoaffinity chromatography, and tandem mass spectrometry and identified Glu-plasminogen sequences containing epitopes recognized by the anti-plasminogen-RIBS mAbs: a linear epitope within a domain linking kringles 1 and 2; a nonlinear epitope contained within the kringle 5 domain and the latent protease domain; and a nonlinear epitope contained within the N-terminal peptide of Glu-plasminogen and the latent protease domain. Our results identify neoepitopes latent in soluble Glu-plasminogen that become available when Glu-plasminogen binds to cells and demonstrate that binding of Glu-plasminogen to cells induces a conformational change in Glu-plasminogen distinct from that of Lys-Pg.

UI MeSH Term Description Entries
D007797 Laminin Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. Merosin,Glycoprotein GP-2,Laminin M,Laminin M Chain,Chain, Laminin M,Glycoprotein GP 2,M Chain, Laminin
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010958 Plasminogen Precursor of plasmin (FIBRINOLYSIN). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. Profibrinolysin,Glu-Plasminogen,Glutamic Acid 1-Plasminogen,Glutamyl Plasminogen,1-Plasminogen, Glutamic Acid,Glu Plasminogen,Glutamic Acid 1 Plasminogen,Plasminogen, Glutamyl
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D011509 Proteoglycans Glycoproteins which have a very high polysaccharide content. Proteoglycan,Proteoglycan Type H
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D003094 Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH). Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen

Related Publications

Jaena Han, and Nagyung Baik, and Kee-Hwan Kim, and Jian-Ming Yang, and Gye Won Han, and Yun Gong, and Mercè Jardí, and Francis J Castellino, and Jordi Felez, and Robert J Parmer, and Lindsey A Miles
July 2012, Blood,
Jaena Han, and Nagyung Baik, and Kee-Hwan Kim, and Jian-Ming Yang, and Gye Won Han, and Yun Gong, and Mercè Jardí, and Francis J Castellino, and Jordi Felez, and Robert J Parmer, and Lindsey A Miles
January 2012, Journal of biomedicine & biotechnology,
Jaena Han, and Nagyung Baik, and Kee-Hwan Kim, and Jian-Ming Yang, and Gye Won Han, and Yun Gong, and Mercè Jardí, and Francis J Castellino, and Jordi Felez, and Robert J Parmer, and Lindsey A Miles
January 1988, Current topics in microbiology and immunology,
Jaena Han, and Nagyung Baik, and Kee-Hwan Kim, and Jian-Ming Yang, and Gye Won Han, and Yun Gong, and Mercè Jardí, and Francis J Castellino, and Jordi Felez, and Robert J Parmer, and Lindsey A Miles
August 1990, The Journal of biological chemistry,
Jaena Han, and Nagyung Baik, and Kee-Hwan Kim, and Jian-Ming Yang, and Gye Won Han, and Yun Gong, and Mercè Jardí, and Francis J Castellino, and Jordi Felez, and Robert J Parmer, and Lindsey A Miles
July 1992, The Biochemical journal,
Jaena Han, and Nagyung Baik, and Kee-Hwan Kim, and Jian-Ming Yang, and Gye Won Han, and Yun Gong, and Mercè Jardí, and Francis J Castellino, and Jordi Felez, and Robert J Parmer, and Lindsey A Miles
September 1990, Planta,
Jaena Han, and Nagyung Baik, and Kee-Hwan Kim, and Jian-Ming Yang, and Gye Won Han, and Yun Gong, and Mercè Jardí, and Francis J Castellino, and Jordi Felez, and Robert J Parmer, and Lindsey A Miles
June 1986, Endocrinology,
Jaena Han, and Nagyung Baik, and Kee-Hwan Kim, and Jian-Ming Yang, and Gye Won Han, and Yun Gong, and Mercè Jardí, and Francis J Castellino, and Jordi Felez, and Robert J Parmer, and Lindsey A Miles
February 1997, Rinsho byori. The Japanese journal of clinical pathology,
Jaena Han, and Nagyung Baik, and Kee-Hwan Kim, and Jian-Ming Yang, and Gye Won Han, and Yun Gong, and Mercè Jardí, and Francis J Castellino, and Jordi Felez, and Robert J Parmer, and Lindsey A Miles
April 1983, Biochemistry,
Jaena Han, and Nagyung Baik, and Kee-Hwan Kim, and Jian-Ming Yang, and Gye Won Han, and Yun Gong, and Mercè Jardí, and Francis J Castellino, and Jordi Felez, and Robert J Parmer, and Lindsey A Miles
April 1997, Thrombosis and haemostasis,
Copied contents to your clipboard!