High-speed atomic force microscopy directly visualizes conformational dynamics of the HIV Vif protein in complex with three host proteins

Yangang Pan, Luda S. Shlyakhtenko, Yuri L. Lyubchenko

Research output: Contribution to journalArticle

Abstract

Vif (viral infectivity factor) is a protein that is essential for the replication of the HIV-1 virus. The key function of Vif is to disrupt the antiviral activity of host APOBEC3 (apolipoprotein B mRNA-editing enzyme catalytic subunit 3) proteins, which mutate viral nucleic acids. Inside the cell, Vif binds to the host cell proteins Elongin-C, Elongin-B, and core-binding factor subunit β, forming a four-protein complex called VCBC. The structure of VCBC-Cullin5 has recently been solved by X-ray crystallography, and, using molecular dynamics simulations, the dynamics of VCBC have been characterized. Here, we applied time-lapse high-speed atomic force microscopy to visualize the conformational changes of the VCBC complex. We determined the three most favorable conformations of this complex, which we identified as the triangle, dumbbell, and globular structures. Moreover, we characterized the dynamics of each of these structures. Our data revealed the very dynamic behavior of all of them, with the triangle and dumbbell structures being the most dynamic. These findings provide insight into the structure and dynamics of the VCBC complex and may support efforts to improve HIV treatment, because Vif is essential for virus survival in the cell.

Original languageEnglish (US)
Pages (from-to)11995-12001
Number of pages7
JournalThe Journal of biological chemistry
Volume295
Issue number34
DOIs
StatePublished - Aug 21 2020

Keywords

  • Elongin-B–CBF-β complex (VCBC)
  • Vif–Elongin-C
  • acquired immune deficiency syndrome (AIDS)
  • double-stranded DNA (dsDNA)
  • high-speed atomic force microscopy (HS-AFM)
  • human APOBEC3 family of cytidine deaminase (APOBEC3) proteins
  • human immunodeficiency virus (HIV)
  • protein assembly
  • protein conformation
  • protein dynamic
  • protein–DNA interaction
  • single-stranded DNA (ssDNA)
  • virus infectivity factor (Vif)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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