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-Structure paper
| タイトル | Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer. |
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| ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 24, Issue 4, Page 370-378, Year 2017 |
| 掲載日 | 2017年2月20日 |
著者 | Qingbo Liu / Priyamvada Acharya / Michael A Dolan / Peng Zhang / Christina Guzzo / Jacky Lu / Alice Kwon / Deepali Gururani / Huiyi Miao / Tatsiana Bylund / Gwo-Yu Chuang / Aliaksandr Druz / Tongqing Zhou / William J Rice / Christoph Wigge / Bridget Carragher / Clinton S Potter / Peter D Kwong / Paolo Lusso / ![]() |
| PubMed 要旨 | Binding of the gp120 envelope (Env) glycoprotein to the CD4 receptor is the first step in the HIV-1 infectious cycle. Although the CD4-binding site has been extensively characterized, the initial ...Binding of the gp120 envelope (Env) glycoprotein to the CD4 receptor is the first step in the HIV-1 infectious cycle. Although the CD4-binding site has been extensively characterized, the initial receptor interaction has been difficult to study because of major CD4-induced structural rearrangements. Here we used cryogenic electron microscopy (cryo-EM) to visualize the initial contact of CD4 with the HIV-1 Env trimer at 6.8-Å resolution. A single CD4 molecule is embraced by a quaternary HIV-1-Env surface formed by coalescence of the previously defined CD4-contact region with a second CD4-binding site (CD4-BS2) in the inner domain of a neighboring gp120 protomer. Disruption of CD4-BS2 destabilized CD4-trimer interaction and abrogated HIV-1 infectivity by preventing the acquisition of coreceptor-binding competence. A corresponding reduction in HIV-1 infectivity occurred after the mutation of CD4 residues that interact with CD4-BS2. Our results document the critical role of quaternary interactions in the initial HIV-Env-receptor contact, with implications for treatment and vaccine design. |
リンク | Nat Struct Mol Biol / PubMed:28218750 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 6.8 Å |
| 構造データ | |
| 由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 Entry early intermediate / CD4 binding site / VIRAL PROTEIN-IMMUNE SYSTEM complex |
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human immunodeficiency virus 1 (ヒト免疫不全ウイルス)
homo sapiens (ヒト)
キーワード