Insight into the HIV-1 Vif SOCS-box-ElonginBC interaction.
The HIV-1 viral infectivity factor (Vif) neutralizes cell-encoded antiviral APOBEC3 proteins by recruiting a cellular ElonginB (EloB)/ElonginC (EloC)/Cullin5-containing ubiquitin ligase complex, resulting in APOBEC3 ubiquitination and proteolysis. The suppressors-of-cytokine-signalling-like domain (SOCS-box) of HIV-1 Vif is essential for E3 ligase engagement, and contains a BC box as well as an unusual proline-rich motif. Here, we report the NMR solution structure of the Vif SOCS-ElonginBC (EloBC) complex. In contrast to SOCS-boxes described in other proteins, the HIV-1 Vif SOCS-box contains only one α-helical domain followed by a β-sheet fold. The SOCS-box of Vif binds primarily to EloC by hydrophobic interactions. The functionally essential proline-rich motif mediates a direct but weak interaction with residues 101-104 of EloB, inducing a conformational change from an unstructured state to a structured state. The structure of the complex and biophysical studies provide detailed insight into the function of Vif's proline-rich motif and reveal novel dynamic information on the Vif-EloBC interaction.
Randall Division of Cell and Molecular Biophysics, King's College London, 3rd Floor, New Hunt's House, Guy's Campus, London Bridge, London SE1 1UL, UK.
Zhisheng
Z
Lu
Julien R C
JR
Bergeron
R Andrew
RA
Atkinson
Torsten
T
Schaller
Dennis A
DA
Veselkov
Alain
A
Oregioni
Yi
Y
Yang
Stephen J
SJ
Matthews
Michael H
MH
Malim
Mark R
MR
Sanderson
D000595:Amino Acid Sequence; D001665:Binding Sites; D044842:Cullin Proteins / Q000737:chemistry / Q000378:metabolism; D000075065:Elongin; D015497:HIV-1 / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011392:Proline / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D050826:Suppressor of Cytokine Signaling Proteins / Q000737:chemistry* / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D044842:Cullin Proteins; C000616396:ELOB protein, human; C000616395:ELOC protein, human; D000075065:Elongin; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D054320:vif Gene Products, Human Immunodeficiency Virus; D011392:Proline
ElonginBC; HIV-1 viral infectivity factor; NMR; SOCS-box domain; solution structure