SOLUTION CONFORMATIONAL PREFERENCES OF IMMUNOGENIC PEPTIDES DERIVED FROM THE PRINCIPAL NEUTRALIZING DETERMINANT OF THE HIV-1 ENVELOPE GLYCOPROTEIN GP120
SOLUTION CONFORMATIONAL PREFERENCES OF IMMUNOGENIC PEPTIDES DERIVED FROM THE PRINCIPAL NEUTRALIZING DETERMINANT OF THE HIV-1 ENVELOPE GLYCOPROTEIN GP120
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DOI：
10.1021/bi00102a009
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发表时间：
1991-09-24
期刊：
影响因子：
2.9
通讯作者：
DYSON, HJ
中科院分区：
文献类型：
--
作者：
CHANDRASEKHAR, K;PROFY, AT;DYSON, HJ
利用标准的一维和二维质子核磁共振技术，在HIV-1的包膜糖蛋白gp120的短肽序列的水溶液中发现了一个共同的结构基序。合成了三个长度为12、24和40个残基的肽（分别称为RP342、RP142和RP70），每个肽含有许多HIV-1分离株共有的中心氨基酸序列。此外，RP70在靠近分子末端的半胱氨酸残基之间含有二硫键，形成一个环，被认为是完整糖蛋白的重要结构和免疫学成分。肽RP70和RP142显示，在保守序列Gly-Pro-Gly-Arg中存在大量含有β -转的构象。在精氨酸的酰胺质子和相邻的甘氨酸之间观察到强核Overhauser效应（NOE）连通性。在脯氨酸残基的c - α - h和精氨酸残基的NH之间观察到弱NOE连通性[A d- α - n (i,i + 2) NOE连通性]，证实了该序列中存在转构象偏好。肽的其余部分显示出构象平均的证据：在水溶液中没有获得任何肽的独特折叠结构的NMR证据。圆二色性（CD）光谱表明，RP70水溶液中不存在有序螺旋，但CD光谱表明，加入三氟乙醇可以诱导约30%的螺旋存在。在TFE/水混合物中，RP70的核磁共振谱发生了与螺旋形成一致的变化，并且明显保留了β转。
With standard one- and two-dimensional proton NMR techniques, a common structural motif has been identified in water solutions of short peptide sequences derived from the envelope glycoprotein gp120 of HIV-1. Three peptides of lengths 12, 24, and 40 residues (termed RP342, RP142, and RP70, respectively) were synthesized, each containing a central amino acid sequence common to many HIV-1 isolates. In addition, RP70 contained a disulfide bond between cysteine residues close to the ends of the molecule, forming a loop that is thought to constitute an important structural and immunological component of the intact glycoprotein. Peptides RP70 and RP142 showed evidence for the presence of a significant population of conformations containing a beta-turn in the conserved sequence Gly-Pro-Gly-Arg. Strong nuclear Overhauser effect (NOE) connectivities were observed between the amide protons of the arginine and the adjacent glycine. A weak NOE connectivity was observed between the C-alpha-H of the proline residue and the NH of the Arg [a d-alpha-N(i,i + 2) NOE connectivity], confirming the presence of a conformational preference for a turn conformation in this sequence. The remainder of the peptide showed evidence of conformational averaging: no NMR evidence for a uniquely folded structure was obtained for any of the peptides in water solution. Circular dichroism (CD) spectra indicated that no ordered helix was present in water solutions of RP70, although a CD spectrum that indicated the presence of approximately 30% helix could be induced by the addition of trifluoroethanol. Changes are observed in the NMR spectrum of RP70 in TFE/water mixtures consistent with helix formation, and the beta-turn is apparently retained.