Monomer-trimer equilibrium of the ectodomain of SIV gp41: Insight into the mechanism of peptide inhibition of HIV infection

Monomer-trimer equilibrium of the ectodomain of SIV gp41: Insight into the mechanism of peptide inhibition of HIV infection
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DOI:
10.1110/ps.8.9.1904
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发表时间:
1999-09-01
期刊:
影响因子:
8
通讯作者:
Clore, GM
Clore, GM
中科院分区:
生物学3区
文献类型:
--
作者:
Caffrey, M;Kaufman, J;Clore, GM

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SIV gp41 胞外域(残基 27-149,e-gp41)的单体-三聚体平衡已通过分析超速离心、圆二色性 (CD) 和 NMR 光谱进行了表征。根据在不同转子速度和蛋白质浓度下进行的分析超速离心实验,STV e-gp41 三聚体的平衡缔合常数为 3.1 X 10(11) M-2。在非变性条件下制备的 C-12 和 C-13 标记的 e-gp41 混合物中分子间核奥弗豪瑟效应的存在明确表明单体和三聚体之间存在动态平衡。 CD 光谱作为 SIV e-gp41 浓度的函数表明单体状态的螺旋含量相对于三聚状态的螺旋含量没有显着变化。讨论了单体-三聚体平衡与 gp41 功能和 gp41 肽的抑制特性的相关性。
The monomer-trimer equilibrium of the ectodomain of SIV gp41 (residues 27-149, e-gp41) has been characterized by analytical ultracentrifugation, circular dichroism (CD), and NMR spectroscopy. Based on analytical ultracentrifugation experiments performed at different rotor speeds and protein concentrations, the equilibrium association constant for the STV e-gp41 trimer is 3.1 X 10(11) M-2. The presence of intermolecular nuclear Overhauser effects in a mixture of C-12 and C-13-labeled e-gp41 prepared under nondenaturing conditions unambiguously demonstrates that there is a dynamic equilibrium between the monomer and trimer. The CD spectra taken as a function of SIV e-gp41 concentration suggest that the helical content of the monomeric state does not change significantly relative to that of the trimeric state. The relevance of the monomer-trimer equilibrium is discussed with respect to gp41 function and the inhibitory properties of gp41 peptides.