Structure and function of the porcine TAP protein and its inhibition by the viral immune evasion protein ICP47.

Han-Ha Chai, Tae-Hun Kim, Young Ran Kim, Dajeong Lim

International journal of biological macromolecules 2021 May 01

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The binding mode to TAP (i.e., the peptide transporter associated with antigen processing) from a viral peptide thus far has been unknown in the field of antiviral immunity, but an interfering mode from a virus-encoded TAP inhibitor has been well documented with respect to blocking the TAP function. In the current study, we predicted the structure of the pig TAP transporter and its inhibition complex by the small viral protein ICP47 of the herpes simplex virus (HSV) encoded by the TAP inhibitor to exploit inhibition of the TAP transporter as the host's immune evasion strategy. We found that the hot spots (residues Leu5, Tyr22, and Leu51) on the ICP47 inhibitor interface tended to prevail over the favored Leu and Tyr, which contributed to significant functional binding at the C-termini recognition principle of the TAP. We further characterized the specificity determinants of the peptide transporter from the pig TAP by the ICP47 inhibitor effects and multidrug TmrAB transporter from the Thermus thermophillus and its immunity regarding its structural homolog of the pig TAP. The specialized structure-function relationship from the pig TAP exporter could provide insight into substrate specificity of the unique immunological properties from the host organism. The TAP disarming capacity from all five viral inhibitors (i.e., the five virus-encoded TAP inhibitors of ICP47, UL49.5, U6, BNLF2a, and CPXV012 proteins) was linked to the infiltration of the TAP functional structure in an unstable conformation and the mounting susceptibility caused by the host's TAP polymorphism. It is anticipated that the functional characterization of the pig TAP transporter based on the pig genomic variants will lead to additional insights into the genotype and single nucleotide polymorphism (SNP) in relation to antiviral resistance and disease susceptibility. Copyright © 2021. Published by Elsevier B.V.

Citation

Han-Ha Chai, Tae-Hun Kim, Young Ran Kim, Dajeong Lim. Structure and function of the porcine TAP protein and its inhibition by the viral immune evasion protein ICP47. International journal of biological macromolecules. 2021 May 01;178:514-526