title: The exon 2b region of the spinal muscular atrophy protein, SMN, is involved in self-association and SIP1 binding.
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.
authors.affiliation: MRIC Biochemistry Group, North East Wales Institute, Mold Road, Wrexham LL11 2AW, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Young
authors.forename: N T
authors.initials: NT
authors.lastname: Man
authors.forename: C L
authors.initials: CL
authors.lastname: Lorson
authors.forename: T T
authors.initials: TT
authors.lastname: Le
authors.forename: E J
authors.initials: EJ
authors.lastname: Androphy
authors.forename: A H
authors.initials: AH
authors.lastname: Burghes
authors.forename: G E
authors.initials: GE
authors.lastname: Morris
mesh_terms: D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D001667:Binding, Competitive; D015374:Biosensing Techniques; D017362:Cyclic AMP Response Element-Binding Protein; D019281:Dimerization; D018604:Epitope Mapping; D005091:Exons / Q000235:genetics*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D055532:SMN Complex Proteins; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D000911:Antibodies, Monoclonal; D017362:Cyclic AMP Response Element-Binding Protein; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D055532:SMN Complex Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2