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8QPA

Cryo-EM Structure of Pre-B+5'ssLNG Complex (core part)

Summary for 8QPA
Entry DOI10.2210/pdb8qpa/pdb
EMDB information18546
DescriptorU5 small nuclear ribonucleoprotein 200 kDa helicase, 116 kDa U5 small nuclear ribonucleoprotein component, NHP2-like protein 1, N-terminally processed, ... (18 entities in total)
Functional Keywordsspliceosome, splicing
Biological sourceHomo sapiens (human)
More
Total number of polymer chains17
Total formula weight1422807.38
Authors
Zhang, Z.,Kumar, V.,Dybkov, O.,Will, C.L.,Zhong, J.,Ludwig, S.,Urlaub, H.,Kastner, B.,Stark, H.,Luehrmann, R. (deposition date: 2023-10-01, release date: 2024-05-22, Last modification date: 2024-07-10)
Primary citationZhang, Z.,Kumar, V.,Dybkov, O.,Will, C.L.,Zhong, J.,Ludwig, S.E.J.,Urlaub, H.,Kastner, B.,Stark, H.,Luhrmann, R.
Structural insights into the cross-exon to cross-intron spliceosome switch.
Nature, 630:1012-1019, 2024
Cited by
PubMed Abstract: Early spliceosome assembly can occur through an intron-defined pathway, whereby U1 and U2 small nuclear ribonucleoprotein particles (snRNPs) assemble across the intron. Alternatively, it can occur through an exon-defined pathway, whereby U2 binds the branch site located upstream of the defined exon and U1 snRNP interacts with the 5' splice site located directly downstream of it. The U4/U6.U5 tri-snRNP subsequently binds to produce a cross-intron (CI) or cross-exon (CE) pre-B complex, which is then converted to the spliceosomal B complex. Exon definition promotes the splicing of upstream introns and plays a key part in alternative splicing regulation. However, the three-dimensional structure of exon-defined spliceosomal complexes and the molecular mechanism of the conversion from a CE-organized to a CI-organized spliceosome, a pre-requisite for splicing catalysis, remain poorly understood. Here cryo-electron microscopy analyses of human CE pre-B complex and B-like complexes reveal extensive structural similarities with their CI counterparts. The results indicate that the CE and CI spliceosome assembly pathways converge already at the pre-B stage. Add-back experiments using purified CE pre-B complexes, coupled with cryo-electron microscopy, elucidate the order of the extensive remodelling events that accompany the formation of B complexes and B-like complexes. The molecular triggers and roles of B-specific proteins in these rearrangements are also identified. We show that CE pre-B complexes can productively bind in trans to a U1 snRNP-bound 5' splice site. Together, our studies provide new mechanistic insights into the CE to CI switch during spliceosome assembly and its effect on pre-mRNA splice site pairing at this stage.
PubMed: 38778104
DOI: 10.1038/s41586-024-07458-1
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.7 Å)
Structure validation

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PDB entries from 2024-11-06

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