Premium
Protein structure and oligomerization are important for the formation of export‐competent HIV‐1 Rev–RRE complexes
Author(s) -
Edgcomb Stephen P.,
Aschrafi Angelique,
Kompfner Elizabeth,
Williamson James R.,
Gerace Larry,
Hennig Mirko
Publication year - 2008
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.073246608
Subject(s) - rna , mutant , messenger rna , nuclear export signal , rna binding protein , microbiology and biotechnology , nucleus , chemistry , viral protein , protein structure , translation (biology) , biology , biophysics , gene , virus , biochemistry , genetics
The translation of the unspliced and partially spliced viral mRNAs that encode the late, structural proteins of HIV‐1 depends on the viral‐protein Rev. Oligomeric binding of Rev to the Rev response element (RRE) in these mRNAs promotes their export from the nucleus and thus controls their expression. Here, we compared the effects of hydrophobic to hydrophilic mutations within the oligomerization domain of Rev using assays for oligomeric RNA binding, protein structure, and export from the nucleus. Oligomeric RNA binding alone does not correlate well with RNA transport activity in the subset of mutants. However, protein structure as judged by CD spectroscopy does correlate well with Rev function. The oligomeric assembly of Rev‐L18T is impaired but exhibits minor defects in structure and retains a basal level of activity in vivo. The prevalence of L18T in infected individuals suggests a positive selection mechanism for L18T modulation of Rev activity that may delay the onset of AIDS.