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-Structure paper
タイトル | Cleavage-independent HIV-1 Env trimers engineered as soluble native spike mimetics for vaccine design. |
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ジャーナル・号・ページ | Cell Rep, Vol. 11, Issue 4, Page 539-550, Year 2015 |
掲載日 | 2015年4月28日 |
著者 | Shailendra Kumar Sharma / Natalia de Val / Shridhar Bale / Javier Guenaga / Karen Tran / Yu Feng / Viktoriya Dubrovskaya / Andrew B Ward / Richard T Wyatt / |
PubMed 要旨 | Viral glycoproteins mediate entry by pH-activated or receptor-engaged activation and exist in metastable pre-fusogenic states that may be stabilized by directed rational design. As recently reported, ...Viral glycoproteins mediate entry by pH-activated or receptor-engaged activation and exist in metastable pre-fusogenic states that may be stabilized by directed rational design. As recently reported, the conformationally fixed HIV-1 envelope glycoprotein (Env) trimers in the pre-fusion state (SOSIP) display molecular homogeneity and structural integrity at relatively high levels of resolution. However, the SOSIPs necessitate full Env precursor cleavage, which requires endogenous furin overexpression. Here, we developed an alternative strategy using flexible peptide covalent linkage of Env subdomains to produce soluble, homogeneous, and cleavage-independent Env mimics, called native flexibly linked (NFL) trimers, as vaccine candidates. This simplified design avoids the need for furin co-expression and, in one case, antibody affinity purification to accelerate trimer scale-up for preclinical and clinical applications. We have successfully translated the NFL design to multiple HIV-1 subtypes, establishing the potential to become a general method of producing native-like, well-ordered Env trimers for HIV-1 or other viruses. |
リンク | Cell Rep / PubMed:25892233 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 17.0 - 23.0 Å |
構造データ | EMDB-6293: EMDB-6294: EMDB-6295: EMDB-6296: EMDB-6297: EMDB-6298: |
由来 |
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