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Tyrosine-sulfated V2 peptides inhibit HIV-1 infection via coreceptor mimicry.

ABSTRACT: Tyrosine sulfation is a post-translational modification that facilitates protein-protein interaction. Two sulfated tyrosines (Tys173 and Tys177) were recently identified within the second variable (V2) loop of the major HIV-1 envelope glycoprotein, gp120, and shown to contribute to stabilizing the intramolecular interaction between V2 and the third variable (V3) loop. Here, we report that tyrosine-sulfated peptides derived from V2 act as structural and functional mimics of the CCR5 N-terminus and potently block HIV-1 infection. Nuclear magnetic and surface plasmon resonance analyses indicate that a tyrosine-sulfated V2 peptide (pV2?-Tys) adopts a CCR5-like helical conformation and directly interacts with gp120 in a CD4-dependent fashion, competing with a CCR5 N-terminal peptide. Sulfated V2 mimics, but not their non-sulfated counterparts, inhibit HIV-1 entry and fusion by preventing coreceptor utilization, with the highly conserved C-terminal sulfotyrosine, Tys177, playing a dominant role. Unlike CCR5 N-terminal peptides, V2 mimics inhibit a broad range of HIV-1 strains irrespective of their coreceptor tropism, highlighting the overall structural conservation of the coreceptor-binding site in gp120. These results document the use of receptor mimicry by a retrovirus to occlude a key neutralization target site and provide leads for the design of therapeutic strategies against HIV-1.

SUBMITTER: Cimbro R

PROVIDER: S-EPMC5006643 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Tyrosine-sulfated V2 peptides inhibit HIV-1 infection via coreceptor mimicry.

Cimbro Raffaello R Peterson Francis C FC Liu Qingbo Q Guzzo Christina C Zhang Peng P Miao Huiyi H Van Ryk Donald D Ambroggio Xavier X Hurt Darrell E DE De Gioia Luca L Volkman Brian F BF Dolan Michael A MA Lusso Paolo P

EBioMedicine 20160626

Tyrosine sulfation is a post-translational modification that facilitates protein-protein interaction. Two sulfated tyrosines (Tys173 and Tys177) were recently identified within the second variable (V2) loop of the major HIV-1 envelope glycoprotein, gp120, and shown to contribute to stabilizing the intramolecular interaction between V2 and the third variable (V3) loop. Here, we report that tyrosine-sulfated peptides derived from V2 act as structural and functional mimics of the CCR5 N-terminus an ...[more]

PMID: 27389109

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Tyrosine-sulfated V2 peptides inhibit HIV-1 infection via coreceptor mimicry.

Publications

Tyrosine-sulfated V2 peptides inhibit HIV-1 infection via coreceptor mimicry.

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