Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
33
|
| pubmed:dateCreated |
1995-9-18
|
| pubmed:abstractText |
Mouse mast cell protease 7 (mMCP-7) is a tryptase stored in the secretory granules of mast cells. At the granule pH of 5.5, mMCP-7 is fully active and is bound to heparin-containing serglycin proteoglycans. to understand the interaction of mMCP-7 with heparin inside and outside the mast cell, this trytase was first studied by comparative protein modeling. The "pro" form of mMCP-7 was then expressed in insect cells and studied by site-directed mutagenesis. Although mMCP-7 lacks known linear sequences of amino acis that interact with heparin, the three-dimensional model of mMCP-7 revealed an area on the surface of the folded protein away from the substrate-binding site that exhibits a strong positive electrostatic potential at the acidic pH of the granule. In agreement with this calculation, recombinant pro-mMCP-7 bound to a heparin-affinity column at pH 5.5 and readily dissociated from the column at pH > 6.5. Site-directed mutagenesis confirmed the prediction that the conversion of His residues 8,68, and 70 in the positively charged region into Glu prevents the binding of pro-mMCP-7 to heparin. Because the binding requires positively charged His residues, native mMCP-7 is able to dissociate from the protease/proteoglycan macromolecular complex when the complex is exocytosed from bone marrow-derived mast cells into a neutral pH environment. Many hematopoietic effector cells store positively charged proteins in granules that contain serglycin proteoglycans. The heparin/mMCP-7 interaction, which depends on the tertiary structure of the tryptase, may be representative of a general control mechanism by which hematopoietic cells maximize storage of properly folded, enzymatically active proteins in their granules.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chymases,
http://linkedlifedata.com/resource/pubmed/chemical/Heparin,
http://linkedlifedata.com/resource/pubmed/chemical/Histidine,
http://linkedlifedata.com/resource/pubmed/chemical/Mcpt6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proteoglycans,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Tpsab1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tryptases,
http://linkedlifedata.com/resource/pubmed/chemical/Vesicular Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/chymase 2,
http://linkedlifedata.com/resource/pubmed/chemical/serglycin
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
18
|
| pubmed:volume |
270
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
19524-31
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:7642636-Amino Acid Sequence,
pubmed-meshheading:7642636-Animals,
pubmed-meshheading:7642636-Base Sequence,
pubmed-meshheading:7642636-Bone Marrow Cells,
pubmed-meshheading:7642636-Cell Line,
pubmed-meshheading:7642636-Chymases,
pubmed-meshheading:7642636-Cytoplasmic Granules,
pubmed-meshheading:7642636-Heparin,
pubmed-meshheading:7642636-Histidine,
pubmed-meshheading:7642636-Mast Cells,
pubmed-meshheading:7642636-Mice,
pubmed-meshheading:7642636-Mice, Inbred BALB C,
pubmed-meshheading:7642636-Molecular Sequence Data,
pubmed-meshheading:7642636-Protein Binding,
pubmed-meshheading:7642636-Proteoglycans,
pubmed-meshheading:7642636-Recombinant Proteins,
pubmed-meshheading:7642636-Sequence Homology, Amino Acid,
pubmed-meshheading:7642636-Serine Endopeptidases,
pubmed-meshheading:7642636-Spodoptera,
pubmed-meshheading:7642636-Tryptases,
pubmed-meshheading:7642636-Vesicular Transport Proteins
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
Packaging of proteases and proteoglycans in the granules of mast cells and other hematopoietic cells. A cluster of histidines on mouse mast cell protease 7 regulates its binding to heparin serglycin proteoglycans.
|
| pubmed:affiliation |
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|