Journal Article

Structure of the Newcastle Disease Virus L protein in complex with tetrameric phosphoprotein

Kang, Huiling, Rao, Zihe, Fu, Wangjun, Chen, Yutao, Feng, Xiaoying, Wang, Lei, Cong, Jingyuan, Wang, Chenlong, Li, Xuemei

2023

Overview

Newcastle disease virus (NDV) belongs to Paramyxoviridae, which contains lethal human and animal pathogens. NDV RNA genome is replicated and transcribed by a multifunctional 250 kDa RNA-dependent RNA polymerase (L protein). To date, high-resolution structure of NDV L protein complexed with P protein remains to be elucidated, limiting our understanding of the molecular mechanisms of Paramyxoviridae replication/transcription. Here, we used cryo-EM and enzymatic assays to investigate the structure-function relationship of L-P complex. We found that C-terminal of CD-MTase-CTD module of the atomic-resolution L-P complex conformationally rearranges, and the priming/intrusion loops are likely in RNA elongation conformations different from previous structures. The P protein adopts a unique tetrameric organization and interacts with L protein. Our findings indicate that NDV L-P complex represents elongation state distinct from previous structures. Our work greatly advances the understanding of Paramyxoviridae RNA synthesis, revealing how initiation/elongation alternates, providing clues for identifying therapeutic targets against Paramyxoviridae. Newcastle disease virus (NDV) belongs to Paramyxoviridae and encodes a large protein (L) and phosphoprotein (P) for viral RNA synthesis. Here the authors present cryo-EM structures of the L-P complex, and propose a model of how RNA initiation/elongation alternates during viral RNA synthesis.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 101/28 / 631/326/596/2148 / 631/535/1258/1259 / 82/80 / 82/83 / Animals / Atomic properties / DNA-directed RNA polymerase / Elongated structure / Elongation / Genomes / Humanities and Social Sciences / Humans / L protein / Molecular modelling / multidisciplinary / Newcastle disease / Newcastle disease virus - genetics / P protein / Paramyxoviridae / Phosphoproteins - metabolism / Priming / Protein structure / Proteins / RNA / RNA polymerase / RNA-Dependent RNA Polymerase - metabolism / RNA-directed RNA polymerase / Science / Science (multidisciplinary) / Structure-function relationships / Synthesis / Therapeutic targets / Transcription / Viral Proteins - metabolism / Viruses