7OP2

Chadox1/ Chimpanzee adenovirus Y25 fiber knob protein

Summary for 7OP2

• Entry DOI: 10.2210/pdb7op2/pdb
• Descriptor: Fiber, CALCIUM ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: fiber knob, viral protein, adenovirus, fiber protein, spike, fiber, chimpanzee adenovirus, simian adenovirus, chadox1, chad-y25, y25, chimp ad, chadv-y25, cell binding, car
• Biological source: Chimpanzee adenovirus Y25
• Total number of polymer chains: 12
• Total formula weight: 248520.78

Authors

Rizkallah, P.J.,Baker, A.T.,Parker, A.L.,Teijeira Crespo, A.,Lipka-Lloyd, M. (deposition date: 2021-05-28, release date: 2021-06-23, Last modification date: 2024-01-31)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.59 Å)