Login / Signup

The herpesvirus UL49.5 protein hijacks a cellular C-degron pathway to drive TAP transporter degradation.

Magda WąchalskaCeleste RiepeMagdalena J ŚlusarzMałgorzata GraulLukasz S BorowskiWenjie QiaoMichalina FoltyńskaJan E CaretteKrystyna Bieńkowska-SzewczykRoman J SzczesnyRon R KopitoAndrea D Lipińska
Published in: Proceedings of the National Academy of Sciences of the United States of America (2024)
The transporter associated with antigen processing (TAP) is a key player in the major histocompatibility class I-restricted antigen presentation and an attractive target for immune evasion by viruses. Bovine herpesvirus 1 impairs TAP-dependent antigenic peptide transport through a two-pronged mechanism in which binding of the UL49.5 gene product to TAP both inhibits peptide transport and triggers its proteasomal degradation. How UL49.5 promotes TAP degradation has, so far, remained unknown. Here, we use high-content siRNA and genome-wide CRISPR-Cas9 screening to identify CLR2 KLHDC3 as the E3 ligase responsible for UL49.5-triggered TAP disposal. We propose that the C terminus of UL49.5 mimics a C-end rule degron that recruits the E3 to TAP and engages the cullin-RING E3 ligase in endoplasmic reticulum-associated degradation.
Keyphrases
  • herpes simplex virus
  • genome wide
  • crispr cas
  • endoplasmic reticulum
  • genome editing
  • heavy metals
  • hyaluronic acid
  • municipal solid waste