4rg5

Publication Abstract from PubMed

The survival motor neuron (SMN) protein forms the oligomeric core of a multi-protein complex required for the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). Deletions and mutations in the SMN1 gene are associated with spinal muscular atrophy (SMA), a devastating neurodegenerative disease that is the leading heritable cause of infant mortality. Oligomerization of SMN is required for its function and some SMA patient mutations disrupt SMN's ability to self-associate. Here, we investigate the oligomeric nature of the SMN.Gemin2 complexes from humans and fission yeast (hSMN.Gemin2 and ySMN.Gemin2). We find that hSMN.Gemin2 forms oligomers spanning the dimer to octamer range. The YG box oligomerization domain of SMN is both necessary and sufficient to form these oligomers. ySMN.Gemin2 exists as a dimer-tetramer equilibrium with Kd = 1.0 +/- 0.9 microM. A 1.9 A crystal structure of the ySMN YG box confirms a high level of structural conservation with the human ortholog in this important region of SMN. Disulfide crosslinking experiments indicate that SMN tetramers are formed by self-association of stable, non-dissociating dimers. Thus, SMN tetramers do not form symmetric helical bundles such as those found in glycine zipper transmembrane oligomers. The dimer-tetramer nature of SMN complexes and the dimer-of-dimers organization of the SMN tetramer provide an important foundation for ongoing studies to understand the mechanism of SMN-assisted snRNP assembly and the underlying causes of SMA.

Oligomeric Properties of Survival Motor Neuron.Gemin2 Complexes.,Gupta K, Martin R, Sharp R, Sarachan KL, Ninan NS, Van Duyne GD J Biol Chem. 2015 Jun 19. pii: jbc.M115.667279. PMID:26092730^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.