Linked Life Data

2964368

Source:http://linkedlifedata.com/resource/pubmed/id/2964368

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1988-4-11
pubmed:abstractText
Using membrane preparations of the interferon receptor, prepared from cells of the Burkitt line, Daudi, we have examined the binding of three human recombinant alpha-interferons. 1. We discovered a binding titration of the interferons IFN-alpha A and IFN-alpha D in the pH range 6-9. Receptor binding, negligible at pH 6, rises to a maximum close to pH 9. We have shown that binding of IFN-alpha A at basic pH is to the same receptors as at neutrality and that IFN-receptor complexes extracted with digitonin are more stable at basic pH than they are at neutrality. 2. The recombinant interferon, IFN-alpha B, shows little change of binding in the pH range 6-9. At its basic optimum the binding of IFN-alpha A approaches that of IFN-alpha B, while at neutral pH the binding of IFN-alpha A is 3-4 times less. This difference at neutral pH is seen on intact cells as well as on membrane preparations. The specific activity of IFN-alpha B is close to that of IFN-alpha A, both of which are 10-20 times more active than IFN-alpha D; and the binding titration is, therefore, independent of the initial binding affinities. 3. Using hybrid IFNs constructed from the DNA sequences of alpha D and alpha B, we have isolated the sequence responsible for the binding titration to the segment comprising amino acids 61-92. Examination of these sequences reveals that Lys-84 is present in all the IFN-alpha except IFN-alpha B where it is replaced by Glu; and Tyr-90, present in most of the common IFN-alpha including alpha A and alpha D, is replaced by Asp in IFN-alpha B. Lys and Tyr would normally titrate in the pH range 6-9. We conclude that the binding titration is due to an electrostatic interaction and we propose that the interaction is between IFN-receptor complexes. The role of the interaction in the binding losses that accompany the antiproliferative effects of IFN is discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
171
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
683-91
pubmed:dateRevised
2007-7-23
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Electrostatic interactions in the cellular dynamics of the interferon-receptor complex.
pubmed:affiliation
Laboratoire d'Oncologie Virale, Institut de Recherches Scientifiques sur le Cancer, Villejuif, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't