ジャーナル: Nat Commun / 年: 2016 タイトル: Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability. 著者: Leopold Kong / Linling He / Natalia de Val / Nemil Vora / Charles D Morris / Parisa Azadnia / Devin Sok / Bin Zhou / Dennis R Burton / Andrew B Ward / Ian A Wilson / Jiang Zhu / 要旨: The trimeric HIV-1 envelope glycoprotein (Env) is critical for host immune recognition and neutralization. Despite advances in trimer design, the roots of Env trimer metastability remain elusive. ...The trimeric HIV-1 envelope glycoprotein (Env) is critical for host immune recognition and neutralization. Despite advances in trimer design, the roots of Env trimer metastability remain elusive. Here we investigate the contribution of two Env regions to metastability. First, we computationally redesign a largely disordered bend in heptad region 1 (HR1) of SOSIP trimers that connects the long, central HR1 helix to the fusion peptide, substantially improving the yield of soluble, well-folded trimers. Structural and antigenic analyses of two distinct HR1 redesigns confirm that redesigned Env closely mimics the native, prefusion trimer with a more stable gp41. Next, we replace the cleavage site between gp120 and gp41 with various linkers in the context of an HR1 redesign. Electron microscopy reveals a potential fusion intermediate state for uncleaved trimers containing short but not long linkers. Together, these results outline a general approach for stabilization of Env trimers from diverse HIV-1 strains.
全体 : CSF trimer post-fusion state or intermediate state bound to PGV04
全体
名称: CSF trimer post-fusion state or intermediate state bound to PGV04
要素
試料: CSF trimer post-fusion state or intermediate state bound to PGV04
タンパク質・ペプチド: CSF
タンパク質・ペプチド: PGV04
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超分子 #1000: CSF trimer post-fusion state or intermediate state bound to PGV04
超分子
名称: CSF trimer post-fusion state or intermediate state bound to PGV04 タイプ: sample / ID: 1000 / 集合状態: Trimer bound to three Fabs / Number unique components: 2
分子量
理論値: 570 KDa
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分子 #1: CSF
分子
名称: CSF / タイプ: protein_or_peptide / ID: 1 詳細: Heterodimer of gp120 and gp41 assembles into a trimer. コピー数: 2 / 集合状態: trimer / 組換発現: Yes