Bovine herpesvirus type 1 (BoHV-1) is a pathogen of cattle responsible for infectious bovine rhinotracheitis. The BoHV-1 UL49.5 is a transmembrane protein that 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. Recently, it has been identified that CRL2^KLHDC3 is responsible for UL49.5-triggered TAP degradation via a C-degron pathway and the presence of the degron sequence does not lead to the degradation of UL49.5 itself. The molecular modeling of KLHDC3 in complexes with four UL49.5 C-terminal decapeptides (one native protein and three mutants) revealed their activity to be closely correlated with the conformation which they adopt in KLHDC3 binding cleft. To analyze the interaction between UL49.5 and KLHDC3 in detail, in this work a total of 3.6 μs long molecular dynamics simulations have been performed. The complete UL49.5-KLHDC3 complexes were embedded into the fully hydrated all-atom lipid membrane model with explicit water molecules. The network of polar interactions has been proposed to be responsible for the recognition and binding of the degron in KLHDC3. The interaction network within the binding pocket appeared to be very similar between two CRL2 substrate receptors: KLHDC3 and KLHDC2.

中文翻译：

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极性相互作用的内在网络负责 CRL2KLHDC3 泛素连接酶与 UL49.5 C 降解决定子的结合

1 型牛疱疹病毒 (BoHV-1) 是导致传染性牛鼻气管炎的牛病原体。 BoHV-1 UL49.5 是一种跨膜蛋白，可与抗原加工 (TAP) 相关的转运蛋白结合，并下调与主要组织相容性复合物 I 类 (MHC-I) 的抗原肽复合物的细胞表面表达。 KLHDC3 是一种含有 kelch 结构域的蛋白 3，也是 cullin2-RING (CRL2) E3 泛素连接酶的底物受体。最近，已经确定CRL2 ^KLHDC3通过C-降解决定子途径负责UL49.5触发的TAP降解，并且降解决定子序列的存在不会导致UL49.5本身的降解。 KLHDC3 与四种 UL49.5 C 端十肽（一种天然蛋白和三种突变体）复合物的分子模型表明，它们的活性与其在 KLHDC3 结合裂口中采用的构象密切相关。为了详细分析 UL49.5 和 KLHDC3 之间的相互作用，在这项工作中进行了总共 3.6 μs 长的分子动力学模拟。将完整的 UL49.5-KLHDC3 复合物嵌入具有明确水分子的完全水合的全原子脂质膜模型中。极性相互作用网络被认为负责 KLHDC3 中降解决定子的识别和结合。两个 CRL2 底物受体 KLHDC3 和 KLHDC2 之间的结合袋内的相互作用网络似乎非常相似。