Features of hydrolysis of specific and nonspecific globular proteins and oligopeptides by antibodies against viral integrase from blood of HIV-infected patients

Biochemistry (Mosc). 2015 Feb;80(2):180-201. doi: 10.1134/S0006297915020054.

Abstract

It was shown previously that, as differentiated from canonical proteases, abzymes against myelin basic protein (MBP) from blood of patients with multiple sclerosis and systemic lupus erythematosus effectively cleaved only MBP, while antibodies (ABs) against integrase (IN) from blood of HIV-infected patients specifically hydrolyzed only IN. In this work, all sites of effective hydrolysis by anti-IN antibodies (IgG and IgM) of 25-mer oligopeptide (OP25) corresponding to MBP were identified using reversed-phase and thin-layer chromatographies and MALDI mass spectrometry. It was found that amino acid sequences of OP25 and other oligopeptides hydrolyzed by anti-MBP abzymes were partially homologous to some fragments of the full sequence of IN. Sequences of IN oligopeptides cleavable by anti-IN abzymes were homologous to some fragments of MBP, but anti-MBP abzymes could not effectively hydrolyze OPs corresponding to IN. The common features of the cleavage sites of OP25 and other oligopeptides hydrolyzed by anti-MBP and anti-IN abzymes were revealed. The literature data on hydrolysis of specific and nonspecific proteins and oligopeptides by abzymes against different protein antigens were analyzed. Overall, the literature data suggest that short OPs, including OP25, mainly interact with light chains of polyclonal ABs, which had lower affinity and specificity to the substrate than intact ABs. However, it seems that anti-IN ABs are the only one example of abzymes capable of hydrolyzing various oligopeptides with high efficiency (within some hours but not days). Possible reasons for the efficient hydrolysis of foreign oligopeptides by anti-IN abzymes from HIV-infected patients are discussed.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Catalytic / immunology
  • Antibodies, Catalytic / metabolism*
  • Chromatography, Thin Layer
  • Female
  • HIV Infections / immunology*
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Integrases / immunology*
  • Integrases / metabolism
  • Male
  • Oligopeptides / metabolism*
  • Proteolysis*
  • Viral Proteins / immunology*
  • Viral Proteins / metabolism
  • Young Adult

Substances

  • Antibodies, Catalytic
  • Immunoglobulin G
  • Immunoglobulin M
  • Oligopeptides
  • Viral Proteins
  • Integrases