Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function

Ferenc Tóth, János Kádas, János András Mótyán, J. Tőzsér

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Abstract

The capsid protein of the human immunodeficiency virus type 1 has been found to be a substrate of the retroviral protease in vitro, and its processing was predicted to be strongly dependent on a pH-induced conformational change. Several protease cleavage sites have been identified within the capsid protein, but the importance of its cleavage by the viral protease at the early phase of infection is controversial. To confirm the relevance of this process, we aimed to design, produce, and characterize mutant capsid proteins, in which the protein susceptibility toward HIV-1 protease is altered without affecting other steps of the viral life cycle. Our results indicate that while the introduced mutations changed the cleavage rate at the mutated sites of the capsid protein by HIV-1 protease, some of them caused only negligible or moderate structural changes (A78V, L189F, and L189I). However, the effects of other mutations (W23A, A77P, and L189P) were dramatic, as assessed by secondary structure determination or cyclophilin A-binding assay. Based on our observations, the L189F mutant capsid remains structurally and functionally unchanged and may therefore be the best candidate for use in studies aimed at better understanding the role of the protease in the early postentry events of viral infection or retrovirus-mediated gene transduction.

Original languageEnglish
JournalFEBS Open Bio
DOIs
Publication statusAccepted/In press - 2016

Keywords

  • Capsid protein
  • Circular dichroism spectroscopy
  • Cyclophilin A
  • HIV-1
  • Human immunodeficiency virus type 1
  • Protease, mutagenesis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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