2LDL

Solution NMR Structure of the HIV-1 Exon Splicing Silencer 3


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 256 
  • Conformers Submitted: 12 
  • 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

Solution Structure of the HIV-1 Exon Splicing Silencer 3.

Levengood, J.D.Rollins, C.Mishler, C.H.Johnson, C.A.Miner, G.Rajan, P.Znosko, B.M.Tolbert, B.S.

(2012) J Mol Biol 415: 680-698

  • DOI: https://doi.org/10.1016/j.jmb.2011.11.034
  • Primary Citation of Related Structures:  
    2LDL

  • PubMed Abstract: 

    Alternative splicing of the human immunodeficiency virus type 1 (HIV-1) genomic RNA is necessary to produce the complete viral protein complement, and aberrations in the splicing pattern impair HIV-1 replication. Genome splicing in HIV-1 is tightly regulated by the dynamic assembly/disassembly of trans host factors with cis RNA control elements. The host protein, heterogeneous nuclear ribonucleoprotein (hnRNP) A1, regulates splicing at several highly conserved HIV-1 3' splice sites by binding 5'-UAG-3' elements embedded within regions containing RNA structure. The physical determinants of hnRNP A1 splice site recognition remain poorly defined in HIV-1, thus precluding a detailed understanding of the molecular basis of the splicing pattern. Here, the three-dimensional structure of the exon splicing silencer 3 (ESS3) from HIV-1 has been determined using NMR spectroscopy. ESS3 adopts a 27-nucleotide hairpin with a 10-bp A-form stem that contains a pH-sensitive A(+)C wobble pair. The seven-nucleotide hairpin loop contains the high-affinity hnRNP-A1-responsive 5'-UAGU-3' element and a proximal 5'-GAU-3' motif. The NMR structure shows that the heptaloop adopts a well-organized conformation stabilized primarily by base stacking interactions reminiscent of a U-turn. The apex of the loop is quasi-symmetric with UA dinucleotide steps from the 5'-GAU-3' and 5'-UAGU-3' motifs stacking on opposite sides of the hairpin. As a step towards understanding the binding mechanism, we performed calorimetric and NMR titrations of several hnRNP A1 subdomains into ESS3. The data show that the UP1 domain forms a high-affinity (K(d)=37.8±1.1 nM) complex with ESS3 via site-specific interactions with the loop.


  • Organizational Affiliation

    Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA.


Macromolecules
Find similar nucleic acids by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains LengthOrganismImage
RNA (27-MER)27Human immunodeficiency virus 1
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 256 
  • Conformers Submitted: 12 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-12-28
    Type: Initial release
  • Version 1.1: 2012-02-08
    Changes: Database references
  • Version 1.2: 2024-05-01
    Changes: Data collection, Database references