Disease relevance of POLD3

• Targeted mutation of the outer membrane protein P66 disrupts attachment of the Lyme disease agent, Borrelia burgdorferi, to integrin alphavbeta3 [1].
• This is, to our knowledge, the first description of the targeted disruption of a candidate B. burgdorferi virulence factor with a known biochemical function that can be quantified, and demonstrates the importance of B. burgdorferi P66 in the attachment of this pathogenic spirochete to a human cell-surface receptor [1].
• We have previously demonstrated that poliovirus establishes a unique way of regulating the protein kinase, namely by inducing the specific degradation of P68 during infection (T. L. Black, B. Safer, A. Hovanessian, and M. G. Katze, J. Virol. 63:2244-2251, 1989) [2].
• A sequence comparison revealed considerable polymorphism of the surface domains of P66 proteins of different Lyme disease-causing Borrelia species [3].
• These sera, however, failed to recognize P66 of B. afzelii and B. garinii, as well as an analog of P66 in the relapsing fever agent, B. hermsii [3].

High impact information on POLD3

• Previous work has shown that during infection by the VAI RNA-negative mutant, dl331, both viral and cellular protein synthesis are inhibited due to phosphorylation of the alpha-subunit of the eukaryotic initiation factor, eIF-2, by the P68 protein kinase [4].
• Long-term phosphate labeling experiments show that the only detectably phosphorylated polypeptide is P68, which contains phosphoserine [5].
• In addition, two proteins of the Drosophila embryonic nuclear matrix, P70 and P68, bind these autoantibodies [6].
• At this stage, P68 was found in both the centromeric regions and the connections between chromosomes [7].
• In fixed cells, P68 was found to shuttle in and out of SC35 domains, forming fibres and granules in a cell-cycle dependent manner [7].

Biological context of POLD3

• Contacts between centromeres and P68 granules were observed during all phases of the cycle but they were most prominent in mitosis [7].
• P68 became membrane associated very rapidly in its biogenesis [8].
• Although viral gene expression was required for P68 degradation, the major poliovirus proteases, 2A and 3C, were found not to be directly involved with P68 proteolysis [2].
• Surface exposure and species specificity of an immunoreactive domain of a 66-kilodalton outer membrane protein (P66) of the Borrelia spp. that cause Lyme disease [3].
• CONCLUSION: Anti-HIV-1 RT using HIV reverse transcriptase P-66 protein test showed that compounds 11, 14, 10 and 13 possessed inhibitory effects against HIV-1 reverse transcriptase (RT), with IC50 29.80, 35.20, 43.77 and 63.76 mumol.L-1, respectively [9].

Anatomical context of POLD3

• P68 behaved as an integral membrane protein associated with the plasma membrane of transformed cells [8].

Analytical, diagnostic and therapeutic context of POLD3

• Based on the radioimmunoassay, three of these polypeptides, P17, P26, and P27, are also the antigens for anti-Sm antisera, whereas P68 is the antigen for anti-RNP antisera [5].
• In immunoblotting, 5 of 17 (29.4%) sera from North American patients with early disseminated or persistent Lyme disease reacted against P66 of B. burgdorferi sensu stricto B31 [3].
• For establishing powerful immunoassays, it was necessary to generate recombinant human P68 antigen as the antigenic target [10].
• Comparable Northern blot analysis clearly demonstrated that the inhibitory sequence X could act on the translation of the P68 mRNA [10].
• We have studied the immune response to a variable surface-exposed loop region of the P66 outer membrane protein from Borrelia burgdorferi sensu lato by using an enzyme immunoassay [11].

References