A lysine-to-arginine change found in natural alleles of the human T-cell lymphotropic/leukemia virus type 1 p12(I) protein greatly influences its stability.
A lysine-to-arginine change found in natural alleles of the human T-cell lymphotropic/leukemia virus type 1 p12(I) protein greatly influences its stability.
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在人类 T 细胞嗜淋巴细胞/白血病病毒 1 型 p12(I) 蛋白的天然等位基因中发现的赖氨酸到精氨酸的变化极大地影响了其稳定性。
DOI：
10.1128/jvi.73.8.6460-6467.1999
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发表时间：
1999
影响因子：
5.4
通讯作者：
Franchini,G
中科院分区：
文献类型：
--
作者：
Trovato,R;Mulloy,JC;Johnson,JM;Takemoto,S;deOliveira,MP;Franchini,G
HTLV-1单一剪接的开放阅读框架I蛋白p12I高度不稳定，似乎是兔持续感染所必需的。在这里，我们证明了p121通过两个假定的亮氨酸拉链结构域形成二聚体，并且其稳定性被特定的蛋白酶体抑制剂增强。P12I是泛素化的，其独特的羧基赖氨酸残基突变为精氨酸极大地提高了其稳定性。有趣的是，对53株独立的HTLV-1毒株的分析发现，在热带痉挛截瘫-HTLV-1相关性脊髓病患者的体外样本中发现的天然p12I等位基因在某些病例中包含88位Lys，而在所有成人T细胞白血病-淋巴瘤(ATLL)病例和健康携带者中，精氨酸一直存在于88位。在热带痉挛截瘫-HTLV相关性脊髓病和ATLL或健康携带者中，这种不同等位基因的明显分离可能与体内相关，因为p12I结合了白细胞介素2受体β和γ链，增加了这两个自然等位基因可能对这些分子的调节产生不同影响的可能性。
The HTLV-1 singly spliced open reading frame I protein, p12I, is highly unstable and appears to be necessary for persistent infection in rabbits. Here we demonstrate that p12Iforms dimers through two putative leucine zipper domains and that its stability is augmented by specific proteasome inhibitors. p12Iis ubiquitylated, and mutations of its unique carboxy-terminus lysine residue to an arginine greatly enhance its stability. Interestingly, analysis of 53 independent HTLV-1 strains revealed that the natural p12Ialleles found in ex vivo samples of tropical spastic paraparesis-HTLV-1-associated myelopathy patients contain a Lys at position 88 in some cases, whereas arginine is consistently found at position 88 in HTLV-1 strains from all adult T-cell leukemia-lymphoma (ATLL) cases and healthy carriers studied. This apparent segregation of different alleles in tropical spastic paraparesis-HTLV-associated myelopathy and ATLL or healthy carriers may be relevant in vivo, since p12Ibinds the interleukin-2 receptor β and γcchains, raising the possibility that the two natural alleles might affect differently the regulation of these molecules.