Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET
| العنوان: | Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET |
|---|---|
| المؤلفون: | Peter D. Kwong, Brennan P. Carman, Andrés Finzi, Dongjun Peng, Walther Mothes, Daniel S. Terry, Joseph Sodroski, Amos B. Smith, Baoshan Zhang, Cameron F. Abrams, Jason Gorman, Michael Farzan, Nick Reichard, Maolin Lu, Utz Ermel, Tongqing Zhou, Luis R. Castillo-Menendez, Akihiro Sugawara, Kevin Wang, Jonathan R. Grover, James Arthos, Scott C. Blanchard, James B. Munro, Michael Chambers, Adrian B. McDermott, Ivana Nikić-Spiegel, Edward A. Lemke, Xiaochu Ma, Matthew R. Gardner, Nirmin Alsahafi |
| المصدر: | Nature |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, chemistry.chemical_classification, Mutation, Multidisciplinary, 030102 biochemistry & molecular biology, Strain (chemistry), viruses, HEK 293 cells, virus diseases, Trimer, medicine.disease_cause, Article, Virus, 3. Good health, 03 medical and health sciences, 030104 developmental biology, Förster resonance energy transfer, Protein structure, chemistry, Biophysics, medicine, Glycoprotein |
| الوصف: | The HIV-1 envelope glycoprotein (Env) trimer mediates cell entry and is conformationally dynamic1-8. Imaging by single-molecule fluorescence resonance energy transfer (smFRET) has revealed that, on the surface of intact virions, mature pre-fusion Env transitions from a pre-triggered conformation (state 1) through a default intermediate conformation (state 2) to a conformation in which it is bound to three CD4 receptor molecules (state 3)8-10. It is currently unclear how these states relate to known structures. Breakthroughs in the structural characterization of the HIV-1 Env trimer have previously been achieved by generating soluble and proteolytically cleaved trimers of gp140 Env that are stabilized by a disulfide bond, an isoleucine-to-proline substitution at residue 559 and a truncation at residue 664 (SOSIP.664 trimers)5,11-18. Cryo-electron microscopy studies have been performed with C-terminally truncated Env of the HIV-1JR-FL strain in complex with the antibody PGT15119. Both approaches have revealed similar structures for Env. Although these structures have been presumed to represent the pre-triggered state 1 of HIV-1 Env, this hypothesis has never directly been tested. Here we use smFRET to compare the conformational states of Env trimers used for structural studies with native Env on intact virus. We find that the constructs upon which extant high-resolution structures are based predominantly occupy downstream conformations that represent states 2 and 3. Therefore, the structure of the pre-triggered state-1 conformation of viral Env that has been identified by smFRET and that is preferentially stabilized by many broadly neutralizing antibodies-and thus of interest for the design of immunogens-remains unknown. |
| تدمد: | 1476-4687 0028-0836 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f66785f30afa4ad33e5181894467368c https://doi.org/10.1038/s41586-019-1101-y |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f66785f30afa4ad33e5181894467368c |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14764687 00280836 |
|---|