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-Structure paper
タイトル | Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies. |
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ジャーナル・号・ページ | Cell Rep, Vol. 37, Issue 5, Page 109922, Year 2021 |
掲載日 | 2021年11月2日 |
著者 | Christopher A Cottrell / Kartik Manne / Rui Kong / Shuishu Wang / Tongqing Zhou / Gwo-Yu Chuang / Robert J Edwards / Rory Henderson / Katarzyna Janowska / Megan Kopp / Bob C Lin / Mark K Louder / Adam S Olia / Reda Rawi / Chen-Hsiang Shen / Justin D Taft / Jonathan L Torres / Nelson R Wu / Baoshan Zhang / Nicole A Doria-Rose / Myron S Cohen / Barton F Haynes / Lawrence Shapiro / Andrew B Ward / Priyamvada Acharya / John R Mascola / Peter D Kwong / |
PubMed 要旨 | Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To ...Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dependent CD4bs antibodies. Antibody CH540-VRC40.01 (named for donor-lineage.clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition. |
リンク | Cell Rep / PubMed:34731616 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.28 - 4.8 Å |
構造データ | EMDB-23312, PDB-7lg6: EMDB-23411: Cryo-EM map of BG505 DS-SOSIP in complex with glycan276-dependent broadly neutralizing antibody VRC40.01 Fab EMDB-23412: Cryo-EM map of BG505 DS-SOSIP in complex with Glycan276-Dependent Broadly Neutralizing Antibody VRC33.01 Fab EMDB-23424: Cryo-EM map of Q23.17_DS-SOSIP in complex with Glycan276-Dependent Broadly Neutralizing Antibody 179NC75 Fab |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM (ウイルス性) / antibody (抗体) / HIV (ヒト免疫不全ウイルス) / SOSIP / Env / VIRAL PROTEIN (ウイルスタンパク質) / VIRAL PROTEIN-IMMUNE SYSTEM complex (ウイルス性) / IMMUNE SYSTEM/VIRAL PROTEIN (免疫系) / BG505 DS-SOSIP / glycan276-dependent / glycan276 / broadly neutralizing antibody (中和抗体) / VRC40.01 Fab / HIV- 1 Env / IMMUNE SYSTEM (免疫系) / IMMUNE SYSTEM-VIRAL PROTEIN complex (免疫系) / VRC33.01 Fab / HIV-1 / 179NC75 Fab |