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Structure paper

TitleStructure of the human activated spliceosome in three conformational states.
Journal, issue, pagesCell Res, Vol. 28, Issue 3, Page 307-322, Year 2018
Publish dateJan 23, 2018
AuthorsXiaofeng Zhang / Chuangye Yan / Xiechao Zhan / Lijia Li / Jianlin Lei / Yigong Shi /
PubMed AbstractDuring each cycle of pre-mRNA splicing, the pre-catalytic spliceosome (B complex) is converted into the activated spliceosome (B complex), which has a well-formed active site but cannot proceed to ...During each cycle of pre-mRNA splicing, the pre-catalytic spliceosome (B complex) is converted into the activated spliceosome (B complex), which has a well-formed active site but cannot proceed to the branching reaction. Here, we present the cryo-EM structure of the human B complex in three distinct conformational states. The EM map allows atomic modeling of nearly all protein components of the U2 small nuclear ribonucleoprotein (snRNP), including three of the SF3a complex and seven of the SF3b complex. The structure of the human B complex contains 52 proteins, U2, U5, and U6 small nuclear RNA (snRNA), and a pre-mRNA. Three distinct conformations have been captured, representing the early, mature, and late states of the human B complex. These complexes differ in the orientation of the Switch loop of Prp8, the splicing factors RNF113A and NY-CO-10, and most components of the NineTeen complex (NTC) and the NTC-related complex. Analysis of these three complexes and comparison with the B and C complexes reveal an ordered flux of components in the B-to-B and the B-to-B transitions, which ultimately prime the active site for the branching reaction.
External linksCell Res / PubMed:29360106 / PubMed Central
MethodsEM (single particle)
Resolution4.9 - 6.5 Å
Structure data

6889

5z56

EMDB-6889, PDB-5z56:
cryo-EM structure of a human activated spliceosome (mature Bact) at 5.1 angstrom.
Method: EM (single particle) / Resolution: 5.1 Å

6890

5z57

EMDB-6890, PDB-5z57:
Cryo-EM structure of the human activated spliceosome (late Bact) at 6.5 angstrom
Method: EM (single particle) / Resolution: 6.5 Å

6891

5z58

EMDB-6891, PDB-5z58:
Cryo-EM structure of a human activated spliceosome (early Bact) at 4.9 angstrom.
Method: EM (single particle) / Resolution: 4.9 Å

Chemicals

ChemComp-IHP:
INOSITOL HEXAKISPHOSPHATE

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-ALA:
ALANINE

Source
  • homo sapiens (human)
  • Human (human)
  • unidentified adenovirus
KeywordsSPLICING / human activated spliceosome / mature Bact / pre-mRNA splicing / spliceosome; cryo-EM structure; activated spliceosome; late Bact complex; pre-mRNA splicing / spliceosome / cryo-EM structure / activated spliceosome / early Bact complex

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