PDBsum entry 6zym

Splicing

PDB id: 6zym

Contents

Protein chains

14 a.a.

1722 a.a.

895 a.a.

224 a.a.

315 a.a.

78 a.a.

299 a.a.

202 a.a.

252 a.a.

195 a.a.

142 a.a.

87 a.a.

30 a.a.

203 a.a.

163 a.a.

325 a.a.

35 a.a.

20 a.a.

56 a.a.

157 a.a.

30 a.a.

DNA/RNA

Ligands

IHP

GTP

Metals

_MG ×5

_ZN ×7

References listed in PDB file

Key reference

• Title: Structural insights into the roles of metazoan-Specific splicing factors in the human step 1 spliceosome.
• Authors: K.Bertram, L.El ayoubi, O.Dybkov, D.E.Agafonov, C.L.Will, K.Hartmuth, H.Urlaub, B.Kastner, H.Stark, R.Lührmann.
• Ref.: Mol Cell, 2020, 80, 127. [DOI no: 10.1016/j.molcel.2020.09.012]
• PubMed id: 33007253

Abstract

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^act to C transition. Structural comparisons with human B^act, C^∗, and P complexes reveal an intricate cascade of RNP rearrangements during splicing catalysis, with intermediate RNP conformations not found in yeast, and additionally elucidate the structural basis for the sequential recruitment of metazoan-specific spliceosomal proteins.