Sulfated polyester interactions with the CD4 molecule and with the third variable loop domain (v3) of gp120 are chemically distinct.
Sulfated polyester interactions with the CD4 molecule and with the third variable loop domain (v3) of gp120 are chemically distinct.
复制标题
硫酸化聚酯与 CD4 分子和 gp120 第三可变环结构域 (v3) 的相互作用在化学上是不同的。
DOI：
10.1089/aid.1992.8.1599
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发表时间：
1992
影响因子：
1.5
通讯作者：
Chess,L
中科院分区：
文献类型：
--
作者：
Lederman,S;Bergmann,JE;Cleary,AM;Yellin,MJ;Fusco,PJ;Chess,L
抑制HIV感染的磺化聚酯(SP)既与CD4分子的gp120结合区相互作用，又与gp120分子的v3结构域环(gp120/v3)相互作用，但这些相互作用对抑制HIVenv介导的融合的作用目前尚不清楚。为了研究SP抑制HIVenv介导的融合的分子机制，我们研究了SP处理对重组痘苗病毒(VPE-16)驱动的包膜病毒介导的CD4+细胞融合以及抗HIV单抗与细胞gp120或纯化的rgp120结合的影响。在抑制env介导的融合方面，SP比中和抗gp120/v3单抗更有效。此外，SP与gp120的v3环相互作用，抑制中和单抗9284的结合，但不抑制与相邻表位结合的中和抗gp120/v3单抗9305的结合。由于SP是多阴离子，我们比较了SP-gp120/v3和SP-CD4相互作用的化学性质。而SP抑制单抗9284与rgp120结合的能力相对独立于盐浓度，而干扰rCD4-rgp120结合的能力则依赖于盐浓度，且在低盐浓度时最大。此外，发现SP-gp120相互作用是可逆的，而SP-rCD4相互作用在低盐条件下是相对不可逆的。这些数据与SP与CD4的相互作用主要是静电作用的观点是一致的，但SP与gp120的相互作用具有复杂的特征，这意味着对蛋白质构象的作用。
Sulfated polyesters (SP) that inhibit HIV infection interact with both the gp120 binding region of CD4 molecules and with the v3 domain loop of gp120 molecules (gp120/v3) but the contributions of these interactions to the inhibition of HIVenv-mediated fusion are presently unclear. In order to characterize the molecular mechanisms by which SP inhibit HIVenv-mediated fusion, we studied the effect of SP treatment on env-mediated fusion of CD4+ cells driven by recombinant vaccinia virus (vPE-16) and on the binding of anti-HIV MAbs to cellular gp120 or purified,rgp120. SP were more effective than neutralizing anti-gp120/v3 MAbs in inhibitingenv-mediated fusion. In addition, SP interacted with the v3 loop of gp120 to inhibit the binding of the neutralizing MAb 9284 but not the binding of 9305, a neutralizing anti-gp120/v3 MAb that binds to an adjacent epitope. Because SP are polyanions, we compared the chemical properties of the SP-gp120/v3 and SP-CD4 interactions. Whereas the ability of SP to inhibit the binding of MAb 9284 andrgp120 was relatively independent of NaCl concentrations, the ability of SP to interfere withrCD4-rgp120 binding depended on the NaCl concentration and was maximal at low NaCl concentrations. In addition, the SP-gp120 interaction was found to be reversible, in contrast to the SP-rCD4 interaction which was previously shown to be relatively irreversible at low salt. These data are consistant with the notions that the interaction of SP with CD4 is primarily electrostatic, but that the interaction of SP with gp120 has complex characteristics that implicate a role for protein conformation.