Source:http://linkedlifedata.com/resource/pubmed/id/10092586
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rdf:type | |
lifeskim:mentions |
umls-concept:C0009498,
umls-concept:C0018284,
umls-concept:C0030946,
umls-concept:C0086418,
umls-concept:C0086597,
umls-concept:C0596235,
umls-concept:C0851827,
umls-concept:C1145667,
umls-concept:C1412936,
umls-concept:C1412937,
umls-concept:C1510827,
umls-concept:C1701901,
umls-concept:C1704675,
umls-concept:C1709061,
umls-concept:C1709450
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pubmed:issue |
14
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pubmed:dateCreated |
1999-4-27
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pubmed:abstractText |
The Ca2+-dependent interaction between complement serine proteases C1r and C1s is mediated by their alpha regions, encompassing the major part of their N-terminal CUB-EGF-CUB (where EGF is epidermal growth factor) module array. In order to define the boundaries of the C1r domain(s) responsible for Ca2+ binding and Ca2+-dependent interaction with C1s and to assess the contribution of individual modules to these functions, the CUB, EGF, and CUB-EGF fragments were expressed in eucaryotic systems or synthesized chemically. Gel filtration studies, as well as measurements of intrinsic Tyr fluorescence, provided evidence that the CUB-EGF pair adopts a more compact conformation in the presence of Ca2+. Ca2+-dependent interaction of intact C1r with C1s was studied using surface plasmon resonance spectroscopy, yielding KD values of 10.9-29.7 nM. The C1r CUB-EGF pair bound immobilized C1s with a higher KD (1.5-1.8 microM), which decreased to 31.4 nM when CUB-EGF was used as the immobilized ligand and C1s was free. Half-maximal binding was obtained at comparable Ca2+ concentrations ranging from 5 microM with intact C1r to 10-16 microM for C1ralpha and CUB-EGF. The isolated CUB and EGF fragments or a CUB + EGF mixture did not bind C1s. These data demonstrate that the C1r CUB-EGF module pair (residues 1-175) is the minimal segment required for high affinity Ca2+ binding and Ca2+-dependent interaction with C1s and indicate that Ca2+ binding induces a more compact folding of the CUB-EGF pair.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Complement C1r,
http://linkedlifedata.com/resource/pubmed/chemical/Complement C1s,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
2
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pubmed:volume |
274
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9149-59
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10092586-Animals,
pubmed-meshheading:10092586-Calcium,
pubmed-meshheading:10092586-Cell Line,
pubmed-meshheading:10092586-Complement C1r,
pubmed-meshheading:10092586-Complement C1s,
pubmed-meshheading:10092586-Epidermal Growth Factor,
pubmed-meshheading:10092586-Humans,
pubmed-meshheading:10092586-Kinetics,
pubmed-meshheading:10092586-Macromolecular Substances,
pubmed-meshheading:10092586-Pichia,
pubmed-meshheading:10092586-Recombinant Proteins,
pubmed-meshheading:10092586-Spectrometry, Fluorescence,
pubmed-meshheading:10092586-Spodoptera,
pubmed-meshheading:10092586-Structure-Activity Relationship
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pubmed:year |
1999
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pubmed:articleTitle |
The N-terminal CUB-epidermal growth factor module pair of human complement protease C1r binds Ca2+ with high affinity and mediates Ca2+-dependent interaction with C1s.
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pubmed:affiliation |
Laboratoire d'Enzymologie Moléculaire, Institut de Biologie Structurale Jean-Pierre Ebel, 41 Avenue des Martyrs, 38027 Grenoble Cedex 1, France. thielens@ibs.ibs.fr
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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