Altered-specificity mutants of the HIV Rev arginine-rich motif-RRE IIB interaction.
HIV Rev
RNA-protein interaction
altered specificity
arginine-rich motif
disordered protein
fitness landscape
neutral evolution
Journal
Journal of molecular recognition : JMR
ISSN: 1099-1352
Titre abrégé: J Mol Recognit
Pays: England
ID NLM: 9004580
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
21
09
2019
revised:
08
12
2019
accepted:
20
12
2019
pubmed:
11
1
2020
medline:
7
8
2021
entrez:
11
1
2020
Statut:
ppublish
Résumé
Arginine-rich motifs (ARMs) bind RNA structures with high affinity and specificity, and the human immunodeficiency virus (HIV) exploits ARM-RNA interactions to regulate its lifecycle. The expression of HIV structural genes relies on recognition between the ARM of its Rev protein and its primary binding site, an internal loop in the viral RNA, the Rev-response element region IIB (IIB). Many functional variants of the Rev ARM-IIB interaction have been discovered, yet how easily it can evolve new specificities is poorly explored. A double mutant of Rev ARM, R35G-N40 V, uses an unknown strategy to recognize IIB. Here, isothermal titration calorimetry and gel shift assays show that the R35G-N40V-IIB interaction has high affinity and specificity in vitro and a larger unfavorable entropy change upon binding than that of wild-type Rev ARM-IIB. In stark contrast with the critical dependence of wild-type Rev on Arg35, Arg39, Asn40, and Arg44, mutational profiling shows R35G-N40V is highly mutable at positions 40 and 44 and dependent on Gly35, Arg38, Arg39, Arg42, and Arg43. Affinity measurements in vitro and reporter assay measurements in vivo are consistent with the wild-type Rev ARM and R35G-N40V maintaining their recognition strategies when binding IIB mutants specific to wild-type Rev ARM and R35G-N40V, respectively. Some single amino acid mutants of wild-type Rev ARM and R35G-N40V have enhanced specificity, recognizing mutant IIBs yet not wild-type IIB. These results provide another example of viral ARM-RNA interactions evolving new specificities with few mutations, consistent with neutral theories of evolution.
Substances chimiques
rev Gene Products, Human Immunodeficiency Virus
0
Arginine
94ZLA3W45F
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2833Informations de copyright
© 2020 John Wiley & Sons Ltd.
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