The iron-responsive element-binding protein: localization of the RNA-binding site to the aconitase active-site cleft.
Proc Natl Acad Sci U S A
; 91(2): 574-8, 1994 Jan 18.
Article
in En
| MEDLINE
| ID: mdl-8290565
ABSTRACT
The iron-responsive element-binding protein (IRE-BP) binds to specific stem-loop RNA structures known as iron-responsive elements (IREs) present in a variety of cellular mRNAs (e.g., those encoding ferritin, erythroid 5-aminolevulinate synthase, and transferrin receptor). Expression of these genes is regulated by interaction with the IRE-BP. The IRE-BP is identical in sequence to cytosolic aconitase, and the function of the protein is determined by the presence or absence of an Fe-S cluster. The protein either functions as an active aconitase when the Fe-S cluster is present or as an RNA-binding protein when the protein lacks this cluster. Aconitase activity and IRE-binding activity are mutually exclusive, and interconversion between the two activities is determined by intracellular Fe concentrations. Mapping of the RNA-binding site of the IRE-BP by UV cross-linking studies defines a major contact site between IRE and protein in the active-site region. Modeling based on probable structural similarities between the previously crystallized mitochondrial aconitase and the IRE-BP predicts that these residues would be accessible to the IRE only were there a major change in the predicted conformation of the protein when cells are iron-depleted.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aconitate Hydratase
/
RNA, Messenger
/
RNA-Binding Proteins
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
1994
Document type:
Article