7SLQ

Cryo-EM structure of 7SK core RNP with circular RNA

  • Classification: RNA BINDING PROTEIN/RNA
  • Organism(s): Homo sapiens
  • Expression System: Escherichia coli BL21(DE3)
  • Mutation(s): No 

  • Deposited: 2021-10-24 Released: 2022-03-30 
  • Deposition Author(s): Yang, Y., Liu, S., Zhou, Z.H., Feigon, J.
  • Funding Organization(s): National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS), National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID), American Heart Association

Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.70 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural basis of RNA conformational switching in the transcriptional regulator 7SK RNP.

Yang, Y.Liu, S.Egloff, S.Eichhorn, C.D.Hadjian, T.Zhen, J.Kiss, T.Zhou, Z.H.Feigon, J.

(2022) Mol Cell 82: 1724

  • DOI: https://doi.org/10.1016/j.molcel.2022.03.001
  • Primary Citation of Related Structures:  
    7SLP, 7SLQ

  • PubMed Abstract: 

    7SK non-coding RNA (7SK) negatively regulates RNA polymerase II (RNA Pol II) elongation by inhibiting positive transcription elongation factor b (P-TEFb), and its ribonucleoprotein complex (RNP) is hijacked by HIV-1 for viral transcription and replication. Methylphosphate capping enzyme (MePCE) and La-related protein 7 (Larp7) constitutively associate with 7SK to form a core RNP, while P-TEFb and other proteins dynamically assemble to form different complexes. Here, we present the cryo-EM structures of 7SK core RNP formed with two 7SK conformations, circular and linear, and uncover a common RNA-dependent MePCE-Larp7 complex. Together with NMR, biochemical, and cellular data, these structures reveal the mechanism of MePCE catalytic inactivation in the core RNP, unexpected interactions between Larp7 and RNA that facilitate a role as an RNP chaperone, and that MePCE-7SK-Larp7 core RNP serves as a scaffold for switching between different 7SK conformations essential for RNP assembly and regulation of P-TEFb sequestration and release.


  • Organizational Affiliation

    Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.


Macromolecules

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
7SK snRNA methylphosphate capping enzyme309Homo sapiensMutation(s): 0 
Gene Names: MEPCEBCDIN3
EC: 2.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for Q7L2J0 (Homo sapiens)
Explore Q7L2J0 
Go to UniProtKB:  Q7L2J0
PHAROS:  Q7L2J0
GTEx:  ENSG00000146834 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ7L2J0
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
La-related protein 7480Homo sapiensMutation(s): 0 
Gene Names: LARP7HDCMA18P
UniProt & NIH Common Fund Data Resources
Find proteins for Q4G0J3 (Homo sapiens)
Explore Q4G0J3 
Go to UniProtKB:  Q4G0J3
PHAROS:  Q4G0J3
GTEx:  ENSG00000174720 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ4G0J3
Sequence Annotations
Expand
  • Reference Sequence
Find similar nucleic acids by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains LengthOrganismImage
Minimal circular 7SK RNAC [auth R]65Homo sapiens
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SAH (Subject of Investigation/LOI)
Query on SAH

Download Ideal Coordinates CCD File 
D [auth A]S-ADENOSYL-L-HOMOCYSTEINE
C14 H20 N6 O5 S
ZJUKTBDSGOFHSH-WFMPWKQPSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.70 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONRELION

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR35GM131901
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesR01AI155170
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01GM071940
American Heart AssociationUnited States20POST35210850

Revision History  (Full details and data files)

  • Version 1.0: 2022-03-30
    Type: Initial release
  • Version 1.1: 2022-04-06
    Changes: Database references
  • Version 1.2: 2022-05-18
    Changes: Database references
  • Version 1.3: 2024-06-05
    Changes: Data collection