The gemin2-binding site on SMN protein: Accessibility to antibody

Lam, Le Thanh; Fuller, Heidi R.; Morris, Glenn E.

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.

Citation

Lam, L. T., Fuller, H. R., & Morris, G. E. (2013). The gemin2-binding site on SMN protein: Accessibility to antibody. Biochemical and Biophysical Research Communications, 438(4), 624-627. https://doi.org/10.1016/j.bbrc.2013.08.005

• Journal Article Type: Article
• Online Publication Date: Aug 9, 2013
• Publication Date: 2013-09
• Deposit Date: Jun 13, 2023
• Journal: Biochemical and Biophysical Research Communications
• Print ISSN: 0006-291X
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 438
• Issue: 4
• Pages: 624-627
• DOI: https://doi.org/10.1016/j.bbrc.2013.08.005
• Keywords: Cell Biology; Molecular Biology; Biochemistry; Biophysics
• Additional Information: This article is maintained by: Elsevier; Article Title: The gemin2-binding site on SMN protein: Accessibility to antibody; Journal Title: Biochemical and Biophysical Research Communications; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.bbrc.2013.08.005; Content Type: article; Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.