8HMY

Cryo-EM structure of the human pre-catalytic TSEN/pre-tRNA complex


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.94 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural basis of pre-tRNA intron removal by human tRNA splicing endonuclease.

Zhang, X.Yang, F.Zhan, X.Bian, T.Xing, Z.Lu, Y.Shi, Y.

(2023) Mol Cell 83: 1328-1339.e4

  • DOI: https://doi.org/10.1016/j.molcel.2023.03.015
  • Primary Citation of Related Structures:  
    8HMY, 8HMZ

  • PubMed Abstract: 

    Removal of the intron from precursor-tRNA (pre-tRNA) is essential in all three kingdoms of life. In humans, this process is mediated by the tRNA splicing endonuclease (TSEN) comprising four subunits: TSEN2, TSEN15, TSEN34, and TSEN54. Here, we report the cryo-EM structures of human TSEN bound to full-length pre-tRNA in the pre-catalytic and post-catalytic states at average resolutions of 2.94 and 2.88 Å, respectively. Human TSEN features an extended surface groove that holds the L-shaped pre-tRNA. The mature domain of pre-tRNA is recognized by conserved structural elements of TSEN34, TSEN54, and TSEN2. Such recognition orients the anticodon stem of pre-tRNA and places the 3'-splice site and 5'-splice site into the catalytic centers of TSEN34 and TSEN2, respectively. The bulk of the intron sequences makes no direct interaction with TSEN, explaining why pre-tRNAs of varying introns can be accommodated and cleaved. Our structures reveal the molecular ruler mechanism of pre-tRNA cleavage by TSEN.


  • Organizational Affiliation

    Research Center for Industries of the Future, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Institute of Biology, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou 310024, Zhejiang, China; Westlake Laboratory of Life Sciences and Biomedicine, 18 Shilongshan Road, Hangzhou 310024, Zhejiang, China. Electronic address: xiaofengzhang@ustc.edu.cn.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
tRNA-splicing endonuclease subunit Sen2485Homo sapiensMutation(s): 1 
Gene Names: TSEN2SEN2
EC: 4.6.1.16
UniProt & NIH Common Fund Data Resources
Find proteins for Q8NCE0 (Homo sapiens)
Explore Q8NCE0 
Go to UniProtKB:  Q8NCE0
PHAROS:  Q8NCE0
GTEx:  ENSG00000154743 
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UniProt GroupQ8NCE0
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
tRNA-splicing endonuclease subunit Sen34330Homo sapiensMutation(s): 1 
Gene Names: TSEN34LENG5SEN34
EC: 4.6.1.16
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Find proteins for Q9BSV6 (Homo sapiens)
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Go to UniProtKB:  Q9BSV6
PHAROS:  Q9BSV6
GTEx:  ENSG00000170892 
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UniProt GroupQ9BSV6
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
tRNA-splicing endonuclease subunit Sen54D [auth C]546Homo sapiensMutation(s): 0 
Gene Names: TSEN54SEN54
UniProt & NIH Common Fund Data Resources
Find proteins for Q7Z6J9 (Homo sapiens)
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Go to UniProtKB:  Q7Z6J9
PHAROS:  Q7Z6J9
GTEx:  ENSG00000182173 
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UniProt GroupQ7Z6J9
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
Chromosome 1 open reading frame 19, isoform CRA_aE [auth D]213Homo sapiensMutation(s): 0 
Gene Names: TSEN15C1orf19hCG_40901
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Find proteins for Q8WW01 (Homo sapiens)
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PHAROS:  Q8WW01
GTEx:  ENSG00000198860 
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UniProt GroupQ8WW01
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
Polyribonucleotide 5'-hydroxyl-kinase Clp1F [auth E]445Homo sapiensMutation(s): 0 
Gene Names: CLP1HEAB
EC: 2.7.1.78
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Find proteins for Q92989 (Homo sapiens)
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Go to UniProtKB:  Q92989
PHAROS:  Q92989
GTEx:  ENSG00000172409 
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UniProt GroupQ92989
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Entity ID: 3
MoleculeChains LengthOrganismImage
Pre-tRNAC [auth T]114Homo sapiens
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Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.94 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Natural Science Foundation of China (NSFC)China--

Revision History  (Full details and data files)

  • Version 1.0: 2023-04-19
    Type: Initial release
  • Version 1.1: 2023-05-03
    Changes: Database references
  • Version 1.2: 2024-05-29
    Changes: Data collection