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The gemin2-binding site on SMN protein: accessibility to antibody.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2013 Sep 06; Vol. 438 (4), pp. 624-7. Date of Electronic Publication: 2013 Aug 09. - Publication Year :
- 2013
-
Abstract
- Reduced levels of SMN (survival-of-motor-neurons) protein are the cause of spinal muscular atrophy, an inherited disorder characterised by loss of motor neurons in early childhood. SMN associates with more than eight other proteins to form an RNA-binding complex involved in assembly of the spliceosome. Two monoclonal antibodies (mAbs), MANSMA1 and MANSMA12, have been widely-used in studies of SMN function and their precise binding sites on SMN have now been identified using a phage-displayed peptide library. The amino-acid residues in SMN required for antibody binding are the same as the five most important contact residues for interaction with gemin2. MANSMA12 immuno-precipitated SMN and gemin2 from HeLa cell extracts as efficiently as mAbs against other SMN epitopes or against gemin2. We explain this by showing that SMN exists as large multimeric complexes. This SMN epitope is highly-conserved and identical in human and mouse. To explain the vigorous immune response when mice are immunised with recombinant SMN alone, we suggest this region is masked by gemin2, or a related protein, throughout development, preventing its recognition as a "self-antigen". The epitope for a third mAb, MANSMA3, has been located to eight amino-acids in the proline-rich domain of SMN.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Animals
Antibodies, Monoclonal analysis
Antibodies, Monoclonal immunology
Binding Sites
Epitope Mapping
HeLa Cells
Humans
Immunoprecipitation
Mice
Models, Molecular
Molecular Sequence Data
Protein Binding
SMN Complex Proteins immunology
SMN Complex Proteins chemistry
SMN Complex Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 438
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 23939045
- Full Text :
- https://doi.org/10.1016/j.bbrc.2013.08.005