Specificity and function of the individual amino acids of an important determinant of human immunodeficiency virus type 1 that induces neutralizing activity.

Specificity and function of the individual amino acids of an important determinant of human immunodeficiency virus type 1 that induces neutralizing activity.
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人类免疫缺陷病毒 1 型重要决定因素的单个氨基酸的特异性和功能,可诱导中和活性。

DOI:
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发表时间:
1989
影响因子:
3.8
通讯作者:
Jaap Goudsmit
Jaap Goudsmit
中科院分区:
医学3区
文献类型:
--
作者:
R. H. Meloen;Rob M. J. Liskamp;Jaap Goudsmit

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人类免疫缺陷病毒 1 型的一个重要抗原决定簇在受感染的人类和黑猩猩中诱导中和活性,先前被定位为 HTLV-IIIB 株(分子克隆 BH10)的外被膜糖蛋白(gp 120)上的氨基酸 307 和 320 之间的九肽以及 HTLV-IIIRF 株的氨基酸 320 至 330 之间的九肽。使用不同的血清,我们发现了不同的反应性九肽,它们重叠并共享一个四肽,GPGR。这种四肽在 HTLV-IIIB 和 HTLV-IIIRF 中是相同的,其两侧的氨基酸在病毒株之间有所不同。由于预计 GPGR 会形成 β 转角,并且两侧有两个可能形成二硫桥的半胱氨酸残基,因此建议 gp120 的这一部分具有发夹样结构。四肽 GPGR 和反应肽位于该结构的顶部,充分暴露于抗体。我们使用源自三种反应性九肽的三组肽类似物(其中两组重叠的HTLV-IIIB菌株和一组HTLV-IIIRF菌株)确定了各个氨基酸在抗体结合中的作用。每组都含有肽类似物,其中每个氨基酸一次一个被所有遗传编码的氨基酸取代。每个九肽中至少有五个连续氨基酸对于抗体结合是必需的。它们包含 GPGR 的氨基酸,可能为病毒提供充足的机会逃避免疫监视。
An important antigenic determinant of human immunodeficiency virus type 1 that induces neutralizing activity in infected humans and chimpanzees was previously mapped with nonapeptides between amino acids 307 and 320 on the external envelope glycoprotein (gp 120) of strain HTLV-IIIB (molecular clone BH10) and amino acids 320 to 330 of strain HTLV-IIIRF. Using different sera we found different reactive nonapeptides that overlapped and shared a tetrapeptide, GPGR. This tetrapeptide, which is the same in HTLV-IIIB and HTLV-IIIRF, is flanked by amino acids that vary between virus strains. Because GPGR is predicted to form a beta-turn and is flanked by two cysteine residues that may form a disulphide bridge, a hairpin-like structure is suggested for this part of gp120. The tetrapeptide GPGR and the reactive peptides are located on top of this structure, well exposed to antibodies. We determined the role of the individual amino acids in antibody binding using three sets of peptide analogues derived from three reactive nonapeptides (two of strain HTLV-IIIB which overlapped and one of strain HTLV-IIIRF). Each set contained peptide analogues in which each amino acid was replaced, one at a time, by all genetically encoded amino acids. At least five consecutive amino acids in each nonapeptide were essential for antibody binding. They include amino acids of GPGR and potentially provide the virus with ample opportunity to escape immune surveillance.
人类和黑猩猩的血脑屏障内人类免疫缺陷病毒抗原和抗体的合成。
DOI: 10.1073/pnas.84.11.3876
发表时间: 1987
影响因子: 11.1
作者:
Goudsmit,J;Epstein,LG;Paul,DA;vanderHelm,HJ;Dawson,GJ;Asher,DM;Yanagihara,R;Wolff,AV;GibbsJr,CJ;Gajdusek,DC
通讯作者: Gajdusek,DC
gp120 的第二个保守结构域对于 HIV 感染性和抗体中和很重要。
DOI: 10.1126/science.2830667
发表时间: 1988
期刊: Science (New York, N.Y.)
影响因子: --
作者:
Ho,DD;Kaplan,JC;Rackauskas,IE;Gurney,ME
通讯作者: Gurney,ME