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

PDB id:

6zym

Name:

Splicing

Title:

Human c complex spliceosome - high-resolution core

Structure:

U2 snrna. Chain: 2. U5 snrna. Chain: 5. U6 snrna. Chain: 6. Corepressor interacting with rbpj 1. Chain: 9. Synonym: cbf1-interacting corepressor,recepin.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: hela s3. Organism_taxid: 9606

Authors:

K.Bertram,B.Kastner

Key ref:

K.Bertram et al. (2020). Structural Insights into the Roles of Metazoan-Specific Splicing Factors in the Human Step 1 Spliceosome. Mol Cell, 80, 127. PubMed id: 33007253 DOI: 10.1016/j.molcel.2020.09.012

Date:

02-Aug-20 Release date: 14-Oct-20

Protein chain

Q86X95  (CIR1_HUMAN) -  Corepressor interacting with RBPJ 1 from Homo sapiens

Seq: 450 a.a.

Struc: 14 a.a.

Protein chain

Q6P2Q9  (PRP8_HUMAN) -  Pre-mRNA-processing-splicing factor 8 from Homo sapiens

Seq: 2335 a.a.

Struc: 1722 a.a.

Protein chain

Q15029  (U5S1_HUMAN) -  116 kDa U5 small nuclear ribonucleoprotein component from Homo sapiens

Seq: 972 a.a.

Struc: 895 a.a.

Protein chain

Q13573  (SNW1_HUMAN) -  SNW domain-containing protein 1 from Homo sapiens

Seq: 536 a.a.

Struc: 224 a.a.

Protein chain

O43660  (PLRG1_HUMAN) -  Pleiotropic regulator 1 from Homo sapiens

Seq: 514 a.a.

Struc: 315 a.a.

Protein chain

O60508  (PRP17_HUMAN) -  Pre-mRNA-processing factor 17 from Homo sapiens

Seq: 579 a.a.

Struc: 78 a.a.

Protein chain

Q96DI7  (SNR40_HUMAN) -  U5 small nuclear ribonucleoprotein 40 kDa protein from Homo sapiens

Seq: 357 a.a.

Struc: 299 a.a.

Protein chain

Q99459  (CDC5L_HUMAN) -  Cell division cycle 5-like protein from Homo sapiens

Seq: 802 a.a.

Struc: 202 a.a.

Protein chain

Q9BZJ0  (CRNL1_HUMAN) -  Crooked neck-like protein 1 from Homo sapiens

Seq: 848 a.a.

Struc: 252 a.a.

Protein chain

Q9NW64  (RBM22_HUMAN) -  Pre-mRNA-splicing factor RBM22 from Homo sapiens

Seq: 420 a.a.

Struc: 195 a.a.

Protein chain

P41223  (BUD31_HUMAN) -  Protein BUD31 homolog from Homo sapiens

Seq: 144 a.a.

Struc: 142 a.a.

Protein chain

Q9P013  (CWC15_HUMAN) -  Spliceosome-associated protein CWC15 homolog from Homo sapiens

Seq: 229 a.a.

Struc: 87 a.a.*

Protein chain

Q9UQ35  (SRRM2_HUMAN) -  Serine/arginine repetitive matrix protein 2 from Homo sapiens

Seq: 2752 a.a.

Struc: 30 a.a.

Protein chain

Q9HCG8  (CWC22_HUMAN) -  Pre-mRNA-splicing factor CWC22 homolog from Homo sapiens

Seq: 908 a.a.

Struc: 203 a.a.

Protein chain

Q9Y3C6  (PPIL1_HUMAN) -  Peptidyl-prolyl cis-trans isomerase-like 1 from Homo sapiens

Seq: 166 a.a.

Struc: 163 a.a.

Protein chain

Q9NW82  (WDR70_HUMAN) -  WD repeat-containing protein 70 from Homo sapiens

Seq: 654 a.a.

Struc: 325 a.a.

Protein chain

Q92620  (PRP16_HUMAN) -  Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 from Homo sapiens

Seq: 1227 a.a.

Struc: 35 a.a.

Protein chain

Q9ULR0  (ISY1_HUMAN) -  Pre-mRNA-splicing factor ISY1 homolog from Homo sapiens

Seq: 285 a.a.

Struc: 20 a.a.

Protein chain

Q9NXE8  (CWC25_HUMAN) -  Pre-mRNA-splicing factor CWC25 homolog from Homo sapiens

Seq: 425 a.a.

Struc: 56 a.a.

Protein chain

Q9BW85  (CCD94_HUMAN) -  Splicing factor YJU2 from Homo sapiens

Seq: 323 a.a.

Struc: 157 a.a.

Protein chain

Q14331  (FRG1_HUMAN) -  Protein FRG1 from Homo sapiens

Seq: 258 a.a.

Struc: 30 a.a.

* PDB and UniProt seqs differ at 33 residue positions (black crosses)

DNA/RNA chains

U-G-G-C-U-A-A-G-A-U-C-A-A-G-U-G-U-A-G-U-A-U-C-U-G-U-U 27 bases

C-U-C-U-G-G-U-U-U-C-U-C-U-U-C-A-G-A-U-C-G-C-A-U-A-A-A-U-C-U-U-U-C-G-C-C-U-U-U- 74 bases

G-U-G-C-U-C-G-C-U-U-C-G-G-C-A-G-C-A-C-A-U-A-U-A-C-U-A-A-A-A-U-U-G-G-A-A-C-G-A- 79 bases

G-U-A-A-G-A-G-C-C-U-A-G-C-A-U-G-U-A-G-A-A-A-U-G-A-U-G-U-C-A-U-A-C-U-U-A-U-C-C- 41 bases

C-G-G-C-C-U-C-C-G-A-A-C-G 13 bases

Enzyme reactions

• Enzyme class 2: Chain V: E.C.5.2.1.8 - peptidylprolyl isomerase.
• Reaction: [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0)
• Enzyme class 3: Chain r: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

ATP (Bound ligand (Het Group name = GTP) matches with 96.88% similarity) + H2O = ADP + phosphate + H(+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.molcel.2020.09.012

Mol Cell 80:127 (2020)

PubMed id: 33007253

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

K.Bertram, L.El Ayoubi, O.Dybkov, D.E.Agafonov, C.L.Will, K.Hartmuth, H.Urlaub, B.Kastner, H.Stark, R.Lührmann.

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.