Structure of the transporter associated with antigen processing trapped by herpes simplex virus

Area of Science:

• Structural Biology
• Immunology
• Virology

Background:

• The transporter associated with antigen processing (TAP) is crucial for cellular immunity, presenting viral peptides to T cells.
• Persistent viruses, like herpes simplex virus (HSV), can evade immune detection by inhibiting TAP function.
• HSV utilizes the viral protein ICP47 to block peptide transport through TAP.

Purpose of the Study:

• To determine the molecular structure of human TAP in complex with HSV's ICP47.
• To elucidate the mechanism by which ICP47 inhibits TAP function and facilitates viral immune evasion.

Main Methods:

• Electron cryo-microscopy (cryo-EM) was employed to resolve the structure of human TAP bound to ICP47.
• The resulting cryo-EM map allowed for high-resolution structural determination to 4.0 Å.

Main Results:

• The structure reveals that ICP47 binds to TAP, trapping it in an inactive conformation.
• Specific interactions between ICP47's helical hairpin and TAP's transmembrane cavity explain the inhibition's potency and specificity.
• This structure provides a detailed molecular basis for HSV's immune evasion strategy.

Conclusions:

• The determined structure offers a clear molecular understanding of how persistent viruses like HSV evade immune surveillance.
• This research provides the first high-resolution structure of TAP, facilitating further mechanistic studies of antigen presentation.