Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
36
|
| pubmed:dateCreated |
1997-10-2
|
| pubmed:abstractText |
Interleukin-3 (IL-3) is a member of the cytokine superfamily that promotes multi-potential hematopoietic cell growth by interacting with a cell surface receptor composed of alpha and beta chains. The newly available three-dimensional structure of a variant of human (h) IL-3 allowed us to evaluate new and existing mutagenesis data and to rationally interpret the structure-function relationship of hIL-3 on a structural basis. The amino acid residues that were identified to be important for hIL-3 activity are grouped into two classes. The first class consists of largely hydrophobic residues required for the structural integrity of the protein, including the residues in IL-3 that are largely conserved among 10 mammalian species. These residues form the core of a scaffold for the second class of more rapidly diverging solvent-exposed residues, likely to be required for interaction with the receptor. Ten important and solvent-exposed residues, Asp21, Gly42, Glu43, Gln45, Asp46, Met49, Arg94, Pro96, Phe113, and Lys116, map to one side of the protein and form a putative binding site for the alpha subunit of the receptor. A model of the IL-3.IL-3 receptor complex based on the human growth hormone (hGH).hGH soluble receptor complex structure suggests that the interface between IL-3 and the IL-3 receptor alpha subunit consists of a cluster of hydrophobic residues flanked by electrostatic interactions. Although the IL-3/IL-3 receptor beta subunit interface cannot be uniquely located due to the lack of sufficient experimental data, several residues of the beta subunit that may interact with Glu22 of IL-3 are proposed. The role of these residues can be tested in future mutagenesis studies to define the interaction between IL-3 and IL-3 receptor beta subunit.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
5
|
| pubmed:volume |
272
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
22630-41
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:9278420-Amino Acid Sequence,
pubmed-meshheading:9278420-Animals,
pubmed-meshheading:9278420-Binding Sites,
pubmed-meshheading:9278420-Humans,
pubmed-meshheading:9278420-Interleukin-3,
pubmed-meshheading:9278420-Models, Molecular,
pubmed-meshheading:9278420-Molecular Sequence Data,
pubmed-meshheading:9278420-Mutagenesis,
pubmed-meshheading:9278420-Receptors, Interleukin-3,
pubmed-meshheading:9278420-Sequence Homology, Amino Acid
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
The receptor binding site of human interleukin-3 defined by mutagenesis and molecular modeling.
|
| pubmed:affiliation |
G. D. Searle and Company, St. Louis, Missouri 63198, USA.
|
| pubmed:publicationType |
Journal Article
|