Trimer enhancement mutation effects on HIV-1 matrix protein binding activities

Ayna Alfadhli, Andrew Mack, Christopher Ritchie, Isabel Cylinder, Logan Harper, Philip R. Tedbury, Eric O. Freed, Eric Barklis

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The HIV-1 matrix (MA) protein is the amino-terminal domain of the HIV-1 precursor Gag (Pr55Gag) protein. MA binds to membranes and RNAs, helps transport Pr55Gag proteins to virus assembly sites at the plasma membranes of infected cells, and facilitates the incorporation of HIV-1 envelope (Env) proteins into virions by virtue of an interaction with the Env protein cytoplasmic tails (CTs). MA has been shown to crystallize as a trimer and to organize on membranes in hexamer lattices. MA mutations that localize to residues near the ends of trimer spokes have been observed to impair Env protein assembly into virus particles, and several of these are suppressed by the 62QR mutation at the hubs of trimer interfaces. We have examined the binding activities of wild-type (WT) MA and 62QR MA variants and found that the 62QR mutation stabilized MA trimers but did not alter the way MA proteins organized on membranes. Relative to WT MA, the 62QR protein showed small effects on membrane and RNA binding. However, 62QR proteins bound significantly better to Env CTs than their WT counterparts, and CT binding efficiencies correlated with trimerization efficiencies. Our data suggest a model in which multivalent binding of trimeric HIV-1 Env proteins to MA trimers contributes to the process of Env virion incorporation.

Original languageEnglish (US)
Pages (from-to)5657-5664
Number of pages8
JournalJournal of Virology
Volume90
Issue number12
DOIs
StatePublished - Jun 1 2016

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protein binding
Human immunodeficiency virus 1
Protein Binding
HIV-1
mutation
Mutation
Proteins
proteins
Virion
virion
Membranes
tail
RNA Transport
gag Gene Products
Virus Assembly
Carrier Proteins
Cell Membrane
RNA
plasma membrane

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Trimer enhancement mutation effects on HIV-1 matrix protein binding activities. / Alfadhli, Ayna; Mack, Andrew; Ritchie, Christopher; Cylinder, Isabel; Harper, Logan; Tedbury, Philip R.; Freed, Eric O.; Barklis, Eric.

In: Journal of Virology, Vol. 90, No. 12, 01.06.2016, p. 5657-5664.

Research output: Contribution to journalArticle

Alfadhli, A, Mack, A, Ritchie, C, Cylinder, I, Harper, L, Tedbury, PR, Freed, EO & Barklis, E 2016, 'Trimer enhancement mutation effects on HIV-1 matrix protein binding activities', Journal of Virology, vol. 90, no. 12, pp. 5657-5664. https://doi.org/10.1128/JVI.00509-16
Alfadhli, Ayna ; Mack, Andrew ; Ritchie, Christopher ; Cylinder, Isabel ; Harper, Logan ; Tedbury, Philip R. ; Freed, Eric O. ; Barklis, Eric. / Trimer enhancement mutation effects on HIV-1 matrix protein binding activities. In: Journal of Virology. 2016 ; Vol. 90, No. 12. pp. 5657-5664.
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