+検索条件
-Structure paper
タイトル | Structure-based design of prefusion-stabilized SARS-CoV-2 spikes. |
---|---|
ジャーナル・号・ページ | Science, Vol. 369, Issue 6510, Page 1501-1505, Year 2020 |
掲載日 | 2020年9月18日 |
![]() | Ching-Lin Hsieh / Jory A Goldsmith / Jeffrey M Schaub / Andrea M DiVenere / Hung-Che Kuo / Kamyab Javanmardi / Kevin C Le / Daniel Wrapp / Alison G Lee / Yutong Liu / Chia-Wei Chou / Patrick O Byrne / Christy K Hjorth / Nicole V Johnson / John Ludes-Meyers / Annalee W Nguyen / Juyeon Park / Nianshuang Wang / Dzifa Amengor / Jason J Lavinder / Gregory C Ippolito / Jennifer A Maynard / Ilya J Finkelstein / Jason S McLellan / ![]() |
PubMed 要旨 | The coronavirus disease 2019 (COVID-19) pandemic has led to accelerated efforts to develop therapeutics and vaccines. A key target of these efforts is the spike (S) protein, which is metastable and ...The coronavirus disease 2019 (COVID-19) pandemic has led to accelerated efforts to develop therapeutics and vaccines. A key target of these efforts is the spike (S) protein, which is metastable and difficult to produce recombinantly. We characterized 100 structure-guided spike designs and identified 26 individual substitutions that increased protein yields and stability. Testing combinations of beneficial substitutions resulted in the identification of HexaPro, a variant with six beneficial proline substitutions exhibiting higher expression than its parental construct (by a factor of 10) as well as the ability to withstand heat stress, storage at room temperature, and three freeze-thaw cycles. A cryo-electron microscopy structure of HexaPro at a resolution of 3.2 angstroms confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). |
![]() | ![]() ![]() ![]() |
手法 | EM (単粒子) |
解像度 | 3.2 - 3.21 Å |
構造データ | EMDB-22221, PDB-6xkl: ![]() EMDB-22222: |
化合物 | ![]() ChemComp-NAG: |
由来 |
|
![]() | VIRAL PROTEIN / SARS-CoV-2 / glycoprotein / fusion protein |