Structural Insights into the Roles of Metazoan-Specific Splicing Factors in the Human Step 1 Spliceosome.


Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
01 10 2020
Historique:
received: 08 05 2020
revised: 08 09 2020
accepted: 09 09 2020
entrez: 2 10 2020
pubmed: 3 10 2020
medline: 21 10 2020
Statut: ppublish

Résumé

Human spliceosomes contain numerous proteins absent in yeast, whose functions remain largely unknown. Here we report a 3D cryo-EM structure of the human spliceosomal C complex at 3.4 Å core resolution and 4.5-5.7 Å at its periphery, and aided by protein crosslinking we determine its molecular architecture. Our structure provides additional insights into the spliceosome's architecture between the catalytic steps of splicing, and how proteins aid formation of the spliceosome's catalytically active RNP (ribonucleoprotein) conformation. It reveals the spatial organization of the metazoan-specific proteins PPWD1, WDR70, FRG1, and CIR1 in human C complexes, indicating they stabilize functionally important protein domains and RNA structures rearranged/repositioned during the B

Identifiants

pubmed: 33007253
pii: S1097-2765(20)30620-1
doi: 10.1016/j.molcel.2020.09.012
pii:
doi:

Substances chimiques

Multiprotein Complexes 0
RNA Splicing Factors 0
Ribonucleoproteins 0
RNA 63231-63-0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

127-139.e6

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing financial interests.

Auteurs

Karl Bertram (K)

Department of Structural Dynamics, MPI for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.

Leyla El Ayoubi (L)

Cellular Biochemistry, MPI for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.

Olexandr Dybkov (O)

Cellular Biochemistry, MPI for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.

Dmitry E Agafonov (DE)

Cellular Biochemistry, MPI for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.

Cindy L Will (CL)

Cellular Biochemistry, MPI for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.

Klaus Hartmuth (K)

Cellular Biochemistry, MPI for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.

Henning Urlaub (H)

Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany; Bioanalytics Group, Institute for Clinical Chemistry, University Medical Center Göttingen, Robert-Koch-Straße 40, 37075 Göttingen, Germany.

Berthold Kastner (B)

Cellular Biochemistry, MPI for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany. Electronic address: b.kastner@mpibpc.mpg.de.

Holger Stark (H)

Department of Structural Dynamics, MPI for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany. Electronic address: hstark1@gwdg.de.

Reinhard Lührmann (R)

Cellular Biochemistry, MPI for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany. Electronic address: reinhard.luehrmann@mpibpc.mpg.de.

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Classifications MeSH