6WCZ

CryoEM structure of full-length ZIKV NS5-hSTAT2 complex

Summary for 6WCZ

• Entry DOI: 10.2210/pdb6wcz/pdb
• EMDB information: 21618
• Descriptor: Signal transducer and activator of transcription 2, Non-structural protein 5, ZINC ION (3 entities in total)
• Functional Keywords: zikv ns5, hstat2, cryoem, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 201274.55

Authors

Boxiao, W.,Stephanie, T.,Kang, Z.,Maria, T.S.,Jian, F.,Jiuwei, L.,Linfeng, G.,Wendan, R.,Yanxiang, C.,Ethan, C.V.,HeaJin, H.,Matthew, J.E.,Sean, E.O.,Adolfo, G.S.,Hong, Z.,Rong, H.,Jikui, S. (deposition date: 2020-03-31, release date: 2020-07-08, Last modification date: 2024-05-29)

Primary citation

Wang, B.,Thurmond, S.,Zhou, K.,Sanchez-Aparicio, M.T.,Fang, J.,Lu, J.,Gao, L.,Ren, W.,Cui, Y.,Veit, E.C.,Hong, H.,Evans, M.J.,O'Leary, S.E.,Garcia-Sastre, A.,Zhou, Z.H.,Hai, R.,Song, J.
Structural basis for STAT2 suppression by flavivirus NS5.
Nat.Struct.Mol.Biol., 27:875-885, 2020

PubMed Abstract: Suppressing cellular signal transducers of transcription 2 (STAT2) is a common strategy that viruses use to establish infections, yet the detailed mechanism remains elusive, owing to a lack of structural information about the viral-cellular complex involved. Here, we report the cryo-EM and crystal structures of human STAT2 (hSTAT2) in complex with the non-structural protein 5 (NS5) of Zika virus (ZIKV) and dengue virus (DENV), revealing two-pronged interactions between NS5 and hSTAT2. First, the NS5 methyltransferase and RNA-dependent RNA polymerase (RdRP) domains form a conserved interdomain cleft harboring the coiled-coil domain of hSTAT2, thus preventing association of hSTAT2 with interferon regulatory factor 9. Second, the NS5 RdRP domain also binds the amino-terminal domain of hSTAT2. Disruption of these ZIKV NS5-hSTAT2 interactions compromised NS5-mediated hSTAT2 degradation and interferon suppression, and viral infection under interferon-competent conditions. Taken together, these results clarify the mechanism underlying the functional antagonism of STAT2 by both ZIKV and DENV.

PubMed: 32778820
DOI: 10.1038/s41594-020-0472-y

Experimental method

ELECTRON MICROSCOPY (4 Å)