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-Structure paper
タイトル | Molecular architecture of native HIV-1 gp120 trimers. |
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ジャーナル・号・ページ | Nature, Vol. 455, Issue 7209, Page 109-113, Year 2008 |
掲載日 | 2008年9月4日 |
著者 | Jun Liu / Alberto Bartesaghi / Mario J Borgnia / Guillermo Sapiro / Sriram Subramaniam / |
PubMed 要旨 | The envelope glycoproteins (Env) of human and simian immunodeficiency viruses (HIV and SIV, respectively) mediate virus binding to the cell surface receptor CD4 on target cells to initiate infection. ...The envelope glycoproteins (Env) of human and simian immunodeficiency viruses (HIV and SIV, respectively) mediate virus binding to the cell surface receptor CD4 on target cells to initiate infection. Env is a heterodimer of a transmembrane glycoprotein (gp41) and a surface glycoprotein (gp120), and forms trimers on the surface of the viral membrane. Using cryo-electron tomography combined with three-dimensional image classification and averaging, we report the three-dimensional structures of trimeric Env displayed on native HIV-1 in the unliganded state, in complex with the broadly neutralizing antibody b12 and in a ternary complex with CD4 and the 17b antibody. By fitting the known crystal structures of the monomeric gp120 core in the b12- and CD4/17b-bound conformations into the density maps derived by electron tomography, we derive molecular models for the native HIV-1 gp120 trimer in unliganded and CD4-bound states. We demonstrate that CD4 binding results in a major reorganization of the Env trimer, causing an outward rotation and displacement of each gp120 monomer. This appears to be coupled with a rearrangement of the gp41 region along the central axis of the trimer, leading to closer contact between the viral and target cell membranes. Our findings elucidate the structure and conformational changes of trimeric HIV-1 gp120 relevant to antibody neutralization and attachment to target cells. |
リンク | Nature / PubMed:18668044 / PubMed Central |
手法 | EM (サブトモグラム平均) / EM (単粒子) |
解像度 | 20.0 Å |
構造データ | EMDB-5018: Molecular Structure of the Native HIV-1 gp120 trimer bound to b12: Spike region EMDB-5019: Molecular Structure of Unliganded Native HIV-1 gp120 trimer: Spike region EMDB-5020: Molecular Structure of the Native HIV-1 gp120 trimer bound to CD4 and 17b: Spike region EMDB-5021: Molecular Structure of the Native HIV-1 gp120 trimer bound to b12: Membrane region |
由来 |
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キーワード | VIRAL PROTEIN (ウイルスタンパク質) / HIV-1 / ENVELOPE GLYCOPROTEIN / IMMUNODEFICIENCY VIRUS / gp120 (Gp120 (HIV)) / AIDS (後天性免疫不全症候群) / Apoptosis (アポトーシス) / Cleavage on pair of basic residues / Coiled coil (コイルドコイル) / Envelope protein (エンベロープ (ウイルス)) / Fusion protein (融合タンパク質) / Host-virus interaction / Lipoprotein (リポタンパク質) / Membrane (生体膜) / Palmitate (パルミチン酸) / Viral immunoevasion / Virion (ウイルス) |