Retrocyclin-2: a potent anti-HIV theta-defensin that forms a cyclic cystine ladder structural motif.
Retrocyclin-2: a potent anti-HIV theta-defensin that forms a cyclic cystine ladder structural motif.
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Retrocyclin-2：一种有效的抗 HIV θ 防御素，形成环状胱氨酸阶梯结构基序。
DOI：
10.1007/978-0-387-73657-0_254
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发表时间：
2009
影响因子：
--
通讯作者：
Craik,DavidJ
中科院分区：
文献类型：
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作者：
Daly,NorelleL;Chen,YiK;Rosengren,KJohan;Marx,UteC;Phillips,MartinL;Waring,AlanJ;Wang,Wei;Lehrer,RobertI;Craik,DavidJ
逆转录细胞周期蛋白是一种具有抗人类免疫缺陷病毒、甲型流感病毒和单纯疱疹病毒活性的头-尾环化θ-防御素。逆转录细胞周期蛋白以高亲和力（Kd= 10-100 nM）结合含碳水化合物的表面分子如gp 120和CD 4，并定位于细胞膜上。第一个发现的θ防御素，恒河猴θ防御素1（RTD-1）是一种在猴白细胞中发现的有效抗菌肽[1]。人骨髓表达与RTD-1前体同源的mRNA [2]，但人mRNA转录物信号序列结构域内的提前终止密码子阻止翻译。因此，人类θ-防御素序列，称为逆转录细胞周期蛋白，被认为是代表表达的假基因。基于人假基因序列和RTD-1加工位点的合成逆转录酶抑制剂已被证明可提供抗HIV-1感染的保护[2]。鉴于其有效的抗病毒活性，不寻常的环状骨架和独特的生物合成模式，确定其结构和生化特性是非常重要的。报道了逆转录细胞周期蛋白的第一个三维结构，即最有效的形式之一，逆转录细胞周期蛋白-2。
Retrocyclins are head-to-tail cyclised θ-defensins with potent activity against human immunodeficiency virus, influenza A and herpes simplex virus. Retrocyclins bind carbohydrate-containing surface molecules such as gp120 and CD4 with high affinity (Kd= 10-100 nM) and are localized on the cell membrane. The first θdefensin discovered, rhesus theta defensin 1 (RTD-1) is a potent antimicrobial peptide found in monkey leucocytes [1]. Human bone marrow expresses mRNA that is homologous to the precursors of RTD-1 [2], but a premature stop codon within the signal sequence domain of the human mRNA transcripts prevents translation. Human θ-defensin sequences, termed retrocyclins, are therefore considered to represent expressed pseudogenes. Synthetic retrocyclins based on the human pseudogene sequences and the processing sites of RTD-1 have been shown to confer protection against HIV-1 infection [2]. Given their potent anti-viral activity, unusual cyclic backbone and unique mode of biosynthesis, determination of the structural and biochemical properties of retrocyclins is of great importance. report the first three-dimensional structure of a retrocyclin, namely one of the most potent forms, retrocyclin-2.