Naotaka Tsutsumi (Avtor), Qianhui Qu (Avtor), Maša Mavri (Avtor), Maibritt S. Baggesen (Avtor), Shoji Maeda (Avtor), Deepa Waghray (Avtor), Christian Berg (Avtor), Brian K. Kobilka (Avtor), Mette Marie Rosenklide (Avtor), Georgios Skiniotis (Avtor), K. Christopher Garcia (Avtor)

Povzetek

Epstein-Barr virus (EBV) encodes a G protein-coupled receptor (GPCR) termed BILF1 that is essential for EBV-mediated immunosuppression and oncogenesis. BILF1 couples with inhibitory G protein (Gi), the major intracellular signaling effector for human chemokine receptors, and exhibits constitutive signaling activity; the ligand(s) for BILF1 are unknown. We studied the origins of BILF1's constitutive activity through structure determination of BILF1 bound to the inhibitory G protein (Gi) heterotrimer. The 3.2-Å resolution cryo-electron microscopy structure revealed an extracellular loop within BILF1 that blocked the typical chemokine binding site, suggesting ligand-autonomous receptor activation. Rather, amino acid substitutions within BILF1 transmembrane regions at hallmark ligand-activated class A GPCR "microswitches" stabilized a constitutively active BILF1 conformation for Gi coupling in a ligand-independent fashion. Thus, the constitutive activity of BILF1 promotes immunosuppression and virulence independent of ligand availability, with implications for the function of GPCRs encoded by related viruses and for therapeutic targeting of EBV.

Ključne besede

Epstein-Barr virus;G protein;G protein-coupled receptor;GPCR;cryo-EM;immune evasion;ligand-indpendent signaling;receptor;signaling;viral GPCR;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL VF - Veterinarska fakulteta
UDK: 636.09:616.9:578
COBISS: 110440195 Povezava se bo odprla v novem oknu
ISSN: 1097-4180
Št. ogledov: 64
Št. prenosov: 31
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarne ključne besede: Epstein-Barr Virus Infections;veterinary;Herpesviridae;Receptors, G-Protein-Coupled;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1405-1416
Letnik: ǂVol. ǂ54
Zvezek: ǂno. ǂ7
Čas izdaje: 2021
DOI: 10.1016/j.immuni.2021.06.001
ID: 15841040