4rg5 | pdb_00004rg5
Crystal Structure of S. Pombe SMN YG-Dimer
Structural highlights
FunctionMALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.SMN_SCHPO The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs (PubMed:20400941, PubMed:33754639, PubMed:10749974). Most spliceosomal snRNPs contain a common set of Sm proteins smb1, smd1, smd2, smd3, sme1, smf1 and smg1 that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core) (By similarity). In the cytosol, the Sm proteins smd1, smd2, sme1, smf1 and smg1 (5Sm) are trapped in an inactive 6S pICln-Sm complex by the chaperone saf5 that controls the assembly of the core snRNP (By similarity). To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from saf5 forming an intermediate (By similarity). Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of smd3 and smb1 to complete assembly of the core snRNP (By similarity). Within the SMN complex, smn1 acts as a structural backbone and together with yip11/gem2 it gathers the Sm complex subunits (PubMed:33754639).[UniProtKB:Q16637][1] [2] [3] Publication Abstract from PubMedThe 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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