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6MCE

Solution structure of HIV-1 TAR with Tat RNA Binding Domain

Summary for 6MCE
Entry DOI10.2210/pdb6mce/pdb
NMR InformationBMRB: 30510
DescriptorTAR RNA, Protein Tat (2 entities in total)
Functional Keywordstranscription, rna binding protein
Biological sourceHuman immunodeficiency virus 1 (Human)
More
Total number of polymer chains2
Total formula weight11815.30
Authors
Pham, V.V.,D'Souza, V.M. (deposition date: 2018-08-31, release date: 2018-10-31, Last modification date: 2024-05-01)
Primary citationPham, V.V.,Salguero, C.,Khan, S.N.,Meagher, J.L.,Brown, W.C.,Humbert, N.,de Rocquigny, H.,Smith, J.L.,D'Souza, V.M.
HIV-1 Tat interactions with cellular 7SK and viral TAR RNAs identifies dual structural mimicry.
Nat Commun, 9:4266-4266, 2018
Cited by
PubMed Abstract: The HIV Tat protein competes with the 7SK:HEXIM interaction to hijack pTEFb from 7SK snRNP and recruit it to the TAR motif on stalled viral transcripts. Here we solve structures of 7SK stemloop-1 and TAR in complex with Tat's RNA binding domain (RBD) to gain insights into this process. We find that 7SK is peppered with arginine sandwich motifs (ASM)-three classical and one with a pseudo configuration. Despite having similar RBDs, the presence of an additional arginine, R52, confers Tat the ability to remodel the pseudo configuration, required for HEXIM binding, into a classical sandwich, thus displacing HEXIM. Tat also uses R52 to remodel the TAR bulge into an ASM whose structure is identical to that of the remodeled ASM in 7SK. Together, our structures reveal a dual structural mimicry wherein viral Tat and TAR have co-opted structural motifs present in cellular HEXIM and 7SK for productive transcription of its genome.
PubMed: 30323330
DOI: 10.1038/s41467-018-06591-6
PDB entries with the same primary citation
Experimental method
SOLUTION NMR
Structure validation

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