| First Author | Li W | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 6 | Pages | e0178519 |
| PubMed ID | 28570645 | Mgi Jnum | J:245188 |
| Mgi Id | MGI:5915441 | Doi | 10.1371/journal.pone.0178519 |
| Citation | Li W (2017) How do SMA-linked mutations of SMN1 lead to structural/functional deficiency of the SMA protein?. PLoS One 12(6):e0178519 |
| abstractText | Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease with dysfunctional alpha-motor neurons in the anterior horn of the spinal cord. SMA is caused by loss ( approximately 95% of SMA cases) or mutation ( approximately 5% of SMA cases) of the survival motor neuron 1 gene SMN1. As the product of SMN1, SMN is a component of the SMN complex, and is also involved in the biosynthesis of the small nuclear ribonucleoproteins (snRNPs), which play critical roles in pre-mRNA splicing in the pathogenesis of SMA. To investigate how SMA-linked mutations of SMN1 lead to structural/functional deficiency of SMN, a set of computational analysis of SMN-related structures were conducted and are described in this article. Of extraordinary interest, the structural analysis highlights three SMN residues (Asp44, Glu134 and Gln136) with SMA-linked missense mutations, which cause disruptions of electrostatic interactions for Asp44, Glu134 and Gln136, and result in three functionally deficient SMA-linked SMN mutants, Asp44Val, Glu134Lys and Gln136Glu. From the computational analysis, it is also possible that SMN's Lys45 and Asp36 act as two electrostatic clips at the SMN-Gemin2 complex structure interface. |
