Abstract
Spinal muscular atrophy (SMA) is caused by mutations in the SMN (survival of motor neurons) gene and there is a correlation between disease severity and levels of functional SMN protein. Studies of structure-function relationships in SMN protein may lead to a better understanding of SMA pathogenesis. Self-association of the spinal muscular atrophy protein, SMN, is important for its function in RNA splicing. Biomolecular interaction analysis core analysis now shows that SMN self-association occurs via SMN regions encoded by exons 2b and 6, that exon 2b encodes a binding site for SMN-interacting protein-1 and that interaction occurs between exon 2- and 4-encoded regions within the SMN monomer. The presence of two separate self-association sites suggests a novel mechanism by which linear oligomers or closed rings might be formed from SMN monomers.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antibodies, Monoclonal / biosynthesis
-
Antibodies, Monoclonal / immunology
-
Binding, Competitive
-
Biosensing Techniques
-
Cyclic AMP Response Element-Binding Protein
-
Dimerization
-
Epitope Mapping
-
Exons / genetics*
-
Homeodomain Proteins / metabolism*
-
Humans
-
Muscular Atrophy, Spinal / genetics*
-
Nerve Tissue Proteins / chemistry*
-
Nerve Tissue Proteins / genetics
-
Nerve Tissue Proteins / immunology
-
Nerve Tissue Proteins / metabolism*
-
Peptide Fragments / metabolism
-
Precipitin Tests
-
Protein Binding
-
Protein Structure, Tertiary
-
RNA-Binding Proteins
-
Recombinant Fusion Proteins / metabolism
-
Repressor Proteins / metabolism*
-
SMN Complex Proteins
-
Zinc Finger E-box Binding Homeobox 2
Substances
-
Antibodies, Monoclonal
-
Cyclic AMP Response Element-Binding Protein
-
Homeodomain Proteins
-
Nerve Tissue Proteins
-
Peptide Fragments
-
RNA-Binding Proteins
-
Recombinant Fusion Proteins
-
Repressor Proteins
-
SMN Complex Proteins
-
ZEB2 protein, human
-
Zinc Finger E-box Binding Homeobox 2