Screening HIV-1 antigenic peptides as receptors for antibodies and CD4 in allosteric nanosensors.
We have analyzed the suitability of six antigenic peptides from several HIV-1 structural proteins (namely gp41, gp120, p17, and p24), as anti-HIV-1 antibody receptors in an allosteric enzymatic biosensor. These peptides were inserted in a solvent-exposed surface of Escherichia coli (E. coli) beta-galactosidase by means of conventional recombinant DNA technology. The resulting enzymes were tested to allosterically respond to sera from HIV-1-infected individuals. Only stretches from gp41 and gp120 envelope proteins were able to transduce the molecular contact signal in the presence of immunoreactive sera. Intriguingly, the enzyme displaying the CD4 binding site segment KQFINMWQEVGKAMYAPP was activated by soluble CD4, suggesting that it produces conformational modifications on the allosteric enzyme as those occurring during antibody-promoted induced fit. This fact is discussed in the context of the design of smart protein drugs and markers targeted to CD4+ cells.
Ferraz
Rosa María
RM
Departament de Matemàtica Aplicada IV, Universitat Politècnica de Catalunya, Campus Nord, Jordi Girona 1-3, 08034 Barcelona, Spain.
Rodríguez-Carmona
Escarlata
E
Ferrer-Miralles
Neus
N
Meyerhans
Andreas
A
Villaverde
Antonio
A
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D015374:Biosensing Techniques / Q000295:instrumentation*; D015704:CD4 Antigens / Q000276:immunology*; D004789:Enzyme Activation; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000032:analysis* / Q000737:chemistry; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D036103:Nanotechnology; D010455:Peptides / Q000032:analysis* / Q000737:chemistry; D011971:Receptors, Immunologic / Q000032:analysis*; D011994:Recombinant Proteins; D001616:beta-Galactosidase
D015704:CD4 Antigens; D015483:HIV Antibodies; D015488:HIV Antigens; D010455:Peptides; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C076613:recombinant soluble CD4; D001616:beta-Galactosidase