5XJR

Crystal Structure of the Gemin2-binding domain of SMN, Gemin2dN39 in Complex with SmD1(1-82)/D2/F/E/G from Human

Summary for 5XJR

• Entry DOI: 10.2210/pdb5xjr/pdb
• Related: 5XJL 5XJQ 5XJS
• Descriptor: Gem-associated protein 2, Small nuclear ribonucleoprotein Sm D1, Small nuclear ribonucleoprotein Sm D2, ... (7 entities in total)
• Functional Keywords: splicing
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 7
• Total formula weight: 83283.17

Authors

Yi, H.,Zhang, R. (deposition date: 2017-05-04, release date: 2018-07-04, Last modification date: 2023-11-22)

Primary citation

Yi, H.,Mu, L.,Shen, C.,Kong, X.,Wang, Y.,Hou, Y.,Zhang, R.
Negative cooperativity between Gemin2 and RNA provides insights into RNA selection and the SMN complex's release in snRNP assembly.
Nucleic Acids Res., 2019

PubMed Abstract: The assembly of snRNP cores, in which seven Sm proteins, D1/D2/F/E/G/D3/B, form a ring around the nonameric Sm site of snRNAs, is the early step of spliceosome formation and essential to eukaryotes. It is mediated by the PMRT5 and SMN complexes sequentially in vivo. SMN deficiency causes neurodegenerative disease spinal muscular atrophy (SMA). How the SMN complex assembles snRNP cores is largely unknown, especially how the SMN complex achieves high RNA assembly specificity and how it is released. Here we show, using crystallographic and biochemical approaches, that Gemin2 of the SMN complex enhances RNA specificity of SmD1/D2/F/E/G via a negative cooperativity between Gemin2 and RNA in binding SmD1/D2/F/E/G. Gemin2, independent of its N-tail, constrains the horseshoe-shaped SmD1/D2/F/E/G from outside in a physiologically relevant, narrow state, enabling high RNA specificity. Moreover, the assembly of RNAs inside widens SmD1/D2/F/E/G, causes the release of Gemin2/SMN allosterically and allows SmD3/B to join. The assembly of SmD3/B further facilitates the release of Gemin2/SMN. This is the first to show negative cooperativity in snRNP assembly, which provides insights into RNA selection and the SMN complex's release. These findings reveal a basic mechanism of snRNP core assembly and facilitate pathogenesis studies of SMA.

PubMed: 31799625
DOI: 10.1093/nar/gkz1135

Experimental method

X-RAY DIFFRACTION (3.12 Å)