Extended binding sites of cyclophilin as revealed by the interaction with HIV‐1 Gag polyprotein derived oligopeptides

Extended binding sites of cyclophilin as revealed by the interaction with HIV‐1 Gag polyprotein derived oligopeptides
复制标题

通过与 HIV-1 Gag 多蛋白衍生寡肽的相互作用揭示了亲环蛋白的扩展结合位点

DOI:
10.1016/0014-5793(96)00972-6
复制
发表时间:
1996
期刊:
影响因子:
3.5
通讯作者:
G. Fischer
G. Fischer
中科院分区:
生物学3区
文献类型:
--
作者:
M. Schutkowski;M. Drewello;Steffen Wöllner;M. Jakob;U. Reimer;G. Scherer;A. Schierhorn;G. Fischer

文献摘要

参考文献

被引文献

相似文献

使用源自人类免疫缺陷病毒 1 型 (HIV-1) 片段的 gag 多蛋白 (Pr55gag) 的寡肽来评估 Pr55gag 与人胞质肽基脯氨酰顺转异构酶 (PPIase) 18 kDa 亲环蛋白 (Cyp18) 复合物的推定结合区域的延伸。五种 N 末端乙酰化、C 末端酰胺化寡肽,含有 1 个 (HIV-1 Gag218–224; 1)、2 个(HIV-1 Gag218–226 和 HIV-1 Gag217−224;分别为 2 和 3)、3 个 (HIV-1 Gag217–226; 4) 或 4 个 (HIV-1 Gag213−237; 5) 个脯氨酸残基被合成。使用标准底物的竞争实验,确定了合成肽与 Cyp18 的结合亲和力。 25 聚体肽 5 的 IC50 值为 184 μM,比缺少一个或多个脯氨酸的肽 1-4 低五倍或更多。在含有其他 PPIase 家族酶的测定中,5 毫摩尔浓度的竞争失败揭示了涉及酶活性位点的 Cyp18 特异性相互作用。在其远紫外圆二色性中,5的水溶液显示出无规卷曲构象的特性,但光谱也与脯氨酸特异性二级结构的小贡献一致。然而,典型的形成左手聚脯氨酸 II 螺旋的富含脯氨酸的肽不会竞争 Cyp18 的活性位点。结果表明,HIV-1 gag 多蛋白的推定结合区域与 Cyp18 的 PPIase 位点具有一定程度的结合亲和力,并且可能在已知的亲环蛋白亚位点特异性上添加了以前未识别的拓扑成分。
Oligopeptides derived from the gag polyprotein (Pr55gag) of human immunodeficiency virus type 1 (HIV‐1) segment were used to evaluate the extension of the putative binding region for the complex of Pr55gagand the human cytosolic peptidyl prolylcisltransisomerase (PPIase) 18 kDa cyclophilin (Cyp18). Five N‐terminally acetylated, C‐terminally amidated oligopeptides containing one (HIV‐1 Gag218–224; 1), two (HIV‐1 Gag218–226and HIV‐1 Gag217−224; 2 and 3, respectively), three (HIV‐1 Gag217–226; 4) or four (HIV‐1 Gag213−237; 5) proline residues were synthesized. Using competition experiments with a standard substrate the binding affinities to Cyp18 of the synthesized peptides were determined. The IC50value of 184 μ.M for the 25‐mer peptide 5 was fivefold or more lower than those of the peptides 1–4 lacking one or more prolines. Failure of competition in assays containing enzymes of other PPIase families by millimolar concentrations of 5 revealed a Cyp18 specific interaction involving the active site of the enzyme. In its far UV circular dichroism, aqueous solutions of 5 display properties of random coil conformation, but spectra were also consistent with a small contribution of proline specific secondary structures. However, a proline‐rich peptide typical of forming left‐handed polyproline II helices did not compete for the active site of Cyp18. The results demonstrate that the putative binding region of HIV‐1 gag polyprotein has a certain degree of binding affinity to the PPIase site of Cyp18, and may add a previously unrecognized topological component to the known subsite specificity of cyclophilins.
研究人唾液富含脯氨酸的糖蛋白中多次出现的肽片段中的顺式/反式脯氨酸异构体。
DOI: 10.1111/j.1399-3011.1991.tb01523.x
发表时间: 1991
期刊: International journal of peptide and protein research
影响因子: --
作者:
Loomis,RE;Gonzalez,M;Loomis,PM
通讯作者: Loomis,PM
DOI: 10.1126/science.7526465
发表时间: 1994-11-18
期刊: SCIENCE
影响因子: 56.9
作者:
FENG, SB;CHEN, JK;SCHREIBER, SL
通讯作者: SCHREIBER, SL
DOI: 10.1021/bi00108a031
发表时间: 1991-06
期刊: Biochemistry
影响因子: 2.9
作者:
J. Kofron;P. Kuzmič;V. Kishore;Esther Colon-Bonilla;D. Rich
通讯作者: J. Kofron;P. Kuzmič;V. Kishore;Esther Colon-Bonilla;D. Rich
通过反相 HPLC、CD 和 NMR 光谱检测催乳素受体富含脯氨酸基序 (PRM) 肽的多个顺反构象异构体。
DOI: 10.1042/bj3150833
发表时间: 1996
期刊: The Biochemical journal
影响因子: --
作者:
O'Neal,KD;Chari,MV;Mcdonald,CH;Cook,RG;Yu-Lee,LY;Morrisett,JD;Shearer,WT
通讯作者: Shearer,WT
线性 23 个残基肽显示出形成不寻常的类天然构象的倾向。
DOI: 10.1080/07391102.1995.10508853
发表时间: 1995
影响因子: 4.4
作者:
Sherman,SA;Gmeiner,WH;Kirnarskiy,L;Perini,F;Ruddon,RW
通讯作者: Ruddon,RW