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Highly Mutable Linker Regions Regulate HIV-1 Rev Function and Stability
by
Yang, Shumin
, Fernandes, Jason D.
, Frankel, Alan D.
, Smith, Cynthia
, Jayaraman, Bhargavi
in
13/106
/ 13/109
/ 38
/ 38/70
/ 631/45
/ 631/45/612/1256
/ 82/80
/ Amino Acid Motifs
/ HEK293 Cells
/ HIV
/ HIV-1 - chemistry
/ HIV-1 - growth & development
/ HIV-1 - metabolism
/ Human immunodeficiency virus
/ Humanities and Social Sciences
/ Humans
/ multidisciplinary
/ Mutation
/ Nuclear transport
/ Protein Domains
/ Protein Stability
/ Proteins
/ rev Gene Products, Human Immunodeficiency Virus - chemistry
/ rev Gene Products, Human Immunodeficiency Virus - genetics
/ rev Gene Products, Human Immunodeficiency Virus - metabolism
/ Science
/ Science (multidisciplinary)
/ Structure-Activity Relationship
/ Structure-function relationships
2019
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Highly Mutable Linker Regions Regulate HIV-1 Rev Function and Stability
by
Yang, Shumin
, Fernandes, Jason D.
, Frankel, Alan D.
, Smith, Cynthia
, Jayaraman, Bhargavi
in
13/106
/ 13/109
/ 38
/ 38/70
/ 631/45
/ 631/45/612/1256
/ 82/80
/ Amino Acid Motifs
/ HEK293 Cells
/ HIV
/ HIV-1 - chemistry
/ HIV-1 - growth & development
/ HIV-1 - metabolism
/ Human immunodeficiency virus
/ Humanities and Social Sciences
/ Humans
/ multidisciplinary
/ Mutation
/ Nuclear transport
/ Protein Domains
/ Protein Stability
/ Proteins
/ rev Gene Products, Human Immunodeficiency Virus - chemistry
/ rev Gene Products, Human Immunodeficiency Virus - genetics
/ rev Gene Products, Human Immunodeficiency Virus - metabolism
/ Science
/ Science (multidisciplinary)
/ Structure-Activity Relationship
/ Structure-function relationships
2019
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Highly Mutable Linker Regions Regulate HIV-1 Rev Function and Stability
by
Yang, Shumin
, Fernandes, Jason D.
, Frankel, Alan D.
, Smith, Cynthia
, Jayaraman, Bhargavi
in
13/106
/ 13/109
/ 38
/ 38/70
/ 631/45
/ 631/45/612/1256
/ 82/80
/ Amino Acid Motifs
/ HEK293 Cells
/ HIV
/ HIV-1 - chemistry
/ HIV-1 - growth & development
/ HIV-1 - metabolism
/ Human immunodeficiency virus
/ Humanities and Social Sciences
/ Humans
/ multidisciplinary
/ Mutation
/ Nuclear transport
/ Protein Domains
/ Protein Stability
/ Proteins
/ rev Gene Products, Human Immunodeficiency Virus - chemistry
/ rev Gene Products, Human Immunodeficiency Virus - genetics
/ rev Gene Products, Human Immunodeficiency Virus - metabolism
/ Science
/ Science (multidisciplinary)
/ Structure-Activity Relationship
/ Structure-function relationships
2019
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Highly Mutable Linker Regions Regulate HIV-1 Rev Function and Stability
Journal Article
Highly Mutable Linker Regions Regulate HIV-1 Rev Function and Stability
2019
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Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/109
/ 38
/ 38/70
/ 631/45
/ 82/80
/ HIV
/ HIV-1 - growth & development
/ Human immunodeficiency virus
/ Humanities and Social Sciences
/ Humans
/ Mutation
/ Proteins
/ rev Gene Products, Human Immunodeficiency Virus - chemistry
/ rev Gene Products, Human Immunodeficiency Virus - genetics
/ rev Gene Products, Human Immunodeficiency Virus - metabolism
/ Science
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