MHC class I ubiquitination by a viral PHD/LAP finger protein
MHC class I ubiquitination by a viral PHD/LAP finger protein
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DOI：
10.1016/s1074-7613(01)00213-8
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发表时间：
2001-10-01
期刊：
影响因子：
32.4
通讯作者：
Stevenson, PG
中科院分区：
文献类型：
--
作者：
Boname, JM;Stevenson, PG
鼠γ-疱疹病毒-68 K3（MK 3）是一种PHD/巨指蛋白，下调主要组织相容性复合体（MHC）I类表达。在转染的细胞系中，MK 3在内质网（ER）膜中表达，在那里它结合新合成的H-2 D（B）糖蛋白的胞质尾区并靶向它们进行降解。蛋白酶体抑制剂阻断降解并导致泛素化H-2D的积累（B）。因为它保留了它的天然构象，所以泛素化先于任何变性或移位到胞质溶胶中。MK 3的PHD/β-指对于H-2D（B）结合不是必需的，但对于其泛素化和降解是必需的。因此，γ-疱疹病毒已经使细胞PHD/PHD基序适应于免疫逃避，显然是为了催化MHC I类泛素化。
The murine gamma -herpesvirus-68 K3 (MK3) is a PHD/LAP finger protein that downregulates major histocompatibility complex (MHC) class I expression. In transfected cell lines, MK3 was expressed in the endoplasmic reticulum (ER) membrane, where it bound the cytoplasmic tail of newly synthesized H-2D(b) glycoproteins and targeted them for degradation. Proteasome inhibitors blocked the degradation and led to an accumulation of ubiquitinated H-2D(b). Because this retained its native conformation, ubiquitination preceded any denaturation or dislocation to the cytosol. The PHD/LAP finger of MK3 was not required for H-2D(b) binding but was essential for its ubiquitination and degradation. Thus, gamma -herpesviruses have adapted the cellular PHD/LAP motif to immune evasion, apparently for the catalysis of MHC class I ubiquitination.