|
Basic Characteristics of Mutations
|
|
Mutation Site
|
P76L |
|
Mutation Site Sentence
|
We tested both Rev L75P and P76L mutants for function in our reporter assay and observed only 60% activity (Fig. 3E), while the corresponding viral spreads were comparable to wild-type Rev, consistent with the CDMS data (Fig. 3F). |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
Rev |
|
Standardized Encoding Gene
|
Rev
|
|
Genotype/Subtype
|
HIV-1 |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Cell line
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
30914719
|
|
Title
|
Highly Mutable Linker Regions Regulate HIV-1 Rev Function and Stability
|
|
Author
|
Jayaraman B,Fernandes JD,Yang S,Smith C,Frankel AD
|
|
Journal
|
Scientific reports
|
|
Journal Info
|
2019 Mar 26;9(1):5139
|
|
Abstract
|
HIV-1 Rev is an essential viral regulatory protein that facilitates the nuclear export of intron-containing viral mRNAs. It is organized into structured, functionally well-characterized motifs joined by less understood linker regions. Our recent competitive deep mutational scanning study confirmed many known constraints in Rev's established motifs, but also identified positions of mutational plasticity, most notably in surrounding linker regions. Here, we probe the mutational limits of these linkers by testing the activities of multiple truncation and mass substitution mutations. We find that these regions possess previously unknown structural, functional or regulatory roles, not apparent from systematic point mutational approaches. Specifically, the N- and C-termini of Rev contribute to protein stability; mutations in a turn that connects the two main helices of Rev have different effects in different contexts; and a linker region which connects the second helix of Rev to its nuclear export sequence has structural requirements for function. Thus, Rev function extends beyond its characterized motifs, and is tuned by determinants within seemingly plastic portions of its sequence. Additionally, Rev's ability to tolerate many of these massive truncations and substitutions illustrates the overall mutational and functional robustness inherent in this viral protein.
|
|
Sequence Data
|
-
|