8.B.25.1.2
GN polyprotein protein product, UL49.5, of 96 aas and 2 TMSs, N- and C-terminal. It is an inhibitor of the transporter associated with antigen processing (TAP) system (TC# 3.A.1.209.1), and it's 3-D structure has been determined (Karska et al. 2019).  UL49.5 contains an extracellular region (residues 1-35) and a transmembrane-intracellular segment (residues 36-75), with a flexible membrane-proximal helical structure in the extracellular part, two short alpha-helices in the transmembrane region, and an unordered structure for the cytoplasmic part. Karska et al. 2019 propose three different orientations of UL49.5 when in complex with TAP.  Bovine herpesvirus type 1 (BoHV-1) is a pathogen of cattle responsible for infectious bovine rhinotracheitis. The BoHV-1 UL49.5 binds to the transporter associated with antigen processing (TAP) and downregulates cell surface expression of the antigenic peptide complexes with the major histocompatibility complex class I (MHC-I). KLHDC3 is a kelch domain-containing protein 3 and a substrate receptor of a cullin2-RING (CRL2) E3 ubiquitin ligase. CRL2^KLHDC3 is responsible for UL49.5-triggered TAP degradation via a C-degron pathway, but the presence of the degron sequence does not lead to the degradation of UL49.5 itself. The network of polar interactions may be responsible for recognition and binding of the degron in KLHDC3. The interaction network within the binding pocket appears to be similar between two CRL2 substrate receptors: KLHDC3 and KLHDC2 (Ślusarz and Lipińska 2024).