7OP2

Chadox1/ Chimpanzee adenovirus Y25 fiber knob protein

7OP2 の概要

• エントリーDOI: 10.2210/pdb7op2/pdb
• 分子名称: Fiber, CALCIUM ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: fiber knob, viral protein, adenovirus, fiber protein, spike, fiber, chimpanzee adenovirus, simian adenovirus, chadox1, chad-y25, y25, chimp ad, chadv-y25, cell binding, car
• 由来する生物種: Chimpanzee adenovirus Y25
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 248520.78

構造登録者

Rizkallah, P.J.,Baker, A.T.,Parker, A.L.,Teijeira Crespo, A.,Lipka-Lloyd, M. (登録日: 2021-05-28, 公開日: 2021-06-23, 最終更新日: 2024-01-31)

主引用文献

Baker, A.T.,Boyd, R.J.,Sarkar, D.,Teijeira-Crespo, A.,Chan, C.K.,Bates, E.,Waraich, K.,Vant, J.,Wilson, E.,Truong, C.D.,Lipka-Lloyd, M.,Fromme, P.,Vermaas, J.,Williams, D.,Machiesky, L.,Heurich, M.,Nagalo, B.M.,Coughlan, L.,Umlauf, S.,Chiu, P.L.,Rizkallah, P.J.,Cohen, T.S.,Parker, A.L.,Singharoy, A.,Borad, M.J.
ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome.
Sci Adv, 7:eabl8213-eabl8213, 2021

PubMed Abstract: Vaccines derived from chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 26 (HAdV-D26), and human adenovirus type 5 (HAdV-C5) are critical in combatting the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic. As part of the largest vaccination campaign in history, ultrarare side effects not seen in phase 3 trials, including thrombosis with thrombocytopenia syndrome (TTS), a rare condition resembling heparin-induced thrombocytopenia (HIT), have been observed. This study demonstrates that all three adenoviruses deployed as vaccination vectors versus SARS-CoV-2 bind to platelet factor 4 (PF4), a protein implicated in the pathogenesis of HIT. We have determined the structure of the ChAdOx1 viral vector and used it in state-of-the-art computational simulations to demonstrate an electrostatic interaction mechanism with PF4, which was confirmed experimentally by surface plasmon resonance. These data confirm that PF4 is capable of forming stable complexes with clinically relevant adenoviruses, an important step in unraveling the mechanisms underlying TTS.

PubMed: 34851659
DOI: 10.1126/sciadv.abl8213

実験手法

X-RAY DIFFRACTION (1.59 Å)