7XRW

Solution structure of T. brucei RAP1


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 90 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

The RRM-mediated RNA binding activity in T. brucei RAP1 is essential for VSG monoallelic expression.

Gaurav, A.K.Afrin, M.Yang, X.Saha, A.Sayeed, S.K.A.Pan, X.Ji, Z.Wong, K.B.Zhang, M.Zhao, Y.Li, B.

(2023) Nat Commun 14: 1576-1576

  • DOI: https://doi.org/10.1038/s41467-023-37307-0
  • Primary Citation of Related Structures:  
    7XRW

  • PubMed Abstract: 

    Trypanosoma brucei is a protozoan parasite that causes human African trypanosomiasis. Its major surface antigen VSG is expressed from subtelomeric loci in a strictly monoallelic manner. We previously showed that the telomere protein TbRAP1 binds dsDNA through its 737 RKRRR 741 patch to silence VSGs globally. How TbRAP1 permits expression of the single active VSG is unknown. Through NMR structural analysis, we unexpectedly identify an RNA Recognition Motif (RRM) in TbRAP1, which is unprecedented for RAP1 homologs. Assisted by the 737 RKRRR 741 patch, TbRAP1 RRM recognizes consensus sequences of VSG 3'UTRs in vitro and binds the active VSG RNA in vivo. Mutating conserved RRM residues abolishes the RNA binding activity, significantly decreases the active VSG RNA level, and derepresses silent VSGs. The competition between TbRAP1's RNA and dsDNA binding activities suggests a VSG monoallelic expression mechanism in which the active VSG's abundant RNA antagonizes TbRAP1's silencing effect, thereby sustaining its full-level expression.


  • Organizational Affiliation

    Center for Gene Regulation in Health and Disease, Department of Biological, Geological, and Environmental Sciences, College of Arts and Sciences, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH, 44115, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Repressor activator protein 1127Trypanosoma bruceiMutation(s): 0 
Gene Names: RAP1
UniProt
Find proteins for Q387L4 (Trypanosoma brucei brucei (strain 927/4 GUTat10.1))
Explore Q387L4 
Go to UniProtKB:  Q387L4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ387L4
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 90 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
The University Grants Committee, Research Grants Council (RGC)Hong Kong--

Revision History  (Full details and data files)

  • Version 1.0: 2023-03-01
    Type: Initial release
  • Version 1.1: 2023-04-05
    Changes: Database references
  • Version 1.2: 2024-05-15
    Changes: Data collection, Database references