The HIV-1 envelope glycoproteins (Env) undergo conformational changes upon interaction of the gp120 exterior glycoprotein with the CD4 receptor. The gp120 inner domain topological layers facilitate the transition of Env to the CD4-bound conformation. CD4 engages gp120 by introducing its phenylalanine 43 (Phe43) in a cavity (“the Phe43 cavity”) located at the interface between the inner and outer gp120 domains. Small CD4-mimetic compounds (CD4mc) can bind within the Phe43 cavity and trigger conformational changes similar to those induced by CD4. Crystal structures of CD4mc in complex with a modified CRF01_AE gp120 core revealed the importance of these gp120 inner domain layers in stabilizing the Phe43 cavity and shaping the CD4 binding site. Our studies reveal a complex interplay between the gp120 inner domain and the Phe43 cavity and generate useful information for the development of more-potent CD4mc.

中文翻译：

---

HIV-1 Env gp120内部结构域可塑造Phe43腔和CD4结合位点。

当gp120外部糖蛋白与CD4受体相互作用时，HIV-1包膜糖蛋白（Env）发生构象变化。gp120内部域拓扑层有助于Env过渡到CD4结合的构象。CD4通过将其苯丙氨酸43（Phe43）引入位于内部和外部gp120结构域之间的界面的腔（“ Phe43腔”）中而与gp120接合。小型CD4模拟化合物（CD4mc）可以结合在Phe43腔内，并触发类似于CD4诱导的构象变化。具有修饰的CRF01_AE gp120核心的CD4mc晶体结构揭示了这些gp120内部结构域层在稳定Phe43腔和塑造CD4结合位点方面的重要性。