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Characterization of a Sulfated Anti-HIV Antibody Using an Expanded Genetic Code.
- Source :
-
Biochemistry [Biochemistry] 2018 May 22; Vol. 57 (20), pp. 2903-2907. Date of Electronic Publication: 2018 May 10. - Publication Year :
- 2018
-
Abstract
- Tyrosine sulfation is a crucial post-translational modification for certain antibodies that neutralize HIV. One of the most neutralizing sulfated anti-HIV antibodies, E51, contains a region in its V <subscript>H</subscript> CDR3 loop with five tyrosine (Tyr) residues, which are hypothesized to be partially or fully sulfated to bind to HIV's gp120 coat protein. However, the gp120-binding contribution of each sulfate or more complex sulfation patterns is unknown. In addition, natural sulfation of Tyr-rich loops usually yields a mixture of multiply sulfated products, complicating attempts to dissect the function of individual E51 sulfoforms with unique sulfation patterns. Here, we use an upgraded expanded genetic code for sulfotyrosine (sY) to express homogeneous E51 sulfoforms containing up to five sulfates. Through characterization of the 32 possible sulfoforms of E51, we show that only a subset of E51 sulfoforms with two, three, or four sYs bind to gp120 with potency similar to that of post-translationally sulfated E51, which we find is a mixture of sulfoforms. We show that sulfation of Tyr100i is necessary for gp120 binding whereas sulfation of Tyr100n is detrimental to binding. These results reveal that gp120 binding by E51 requires very specific sulfation patterns and should aid in the further design of sulfated E51-based peptides and immunoadhesins against HIV.
- Subjects :
- Anti-HIV Agents chemistry
Anti-HIV Agents pharmacology
Antibodies, Neutralizing chemistry
Genetic Code genetics
HIV Envelope Protein gp120 antagonists & inhibitors
HIV Envelope Protein gp120 genetics
HIV Infections genetics
HIV Infections virology
HIV-1 genetics
HIV-1 pathogenicity
Humans
Protein Binding
Tyrosine analogs & derivatives
Tyrosine chemistry
Tyrosine genetics
Antibodies, Neutralizing pharmacology
HIV Envelope Protein gp120 immunology
HIV Infections drug therapy
HIV-1 drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4995
- Volume :
- 57
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 29738662
- Full Text :
- https://doi.org/10.1021/acs.biochem.8b00374