6U5O

Structure of the Human Metapneumovirus Polymerase bound to the phosphoprotein tetramer

6U5O の概要

• エントリーDOI: 10.2210/pdb6u5o/pdb
• EMDBエントリー: 20651
• 分子名称: RNA-directed RNA polymerase L, Phosphoprotein (2 entities in total)
• 機能のキーワード: human metapneumovirus, hmpv, polymerase, phosphoprotein, respiratory syncytial virus, rsv, pneumoviridae, mononegavirales, viral protein
• 由来する生物種: Human metapneumovirus (strain CAN97-83) (HMPV); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 376629.83

構造登録者

Pan, J.,Qian, X.,Lattmann, S.,Sahili, A.E.,Yeo, T.H.,Kalocsay, M.,Fearns, R.,Lescar, J. (登録日: 2019-08-28, 公開日: 2019-09-25, 最終更新日: 2025-05-14)

主引用文献

Pan, J.,Qian, X.,Lattmann, S.,El Sahili, A.,Yeo, T.H.,Jia, H.,Cressey, T.,Ludeke, B.,Noton, S.,Kalocsay, M.,Fearns, R.,Lescar, J.
Structure of the human metapneumovirus polymerase phosphoprotein complex.
Nature, 577:275-279, 2020

PubMed Abstract: Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) cause severe respiratory diseases in infants and elderly adults. No vaccine or effective antiviral therapy currently exists to control RSV or HMPV infections. During viral genome replication and transcription, the tetrameric phosphoprotein P serves as a crucial adaptor between the ribonucleoprotein template and the L protein, which has RNA-dependent RNA polymerase (RdRp), GDP polyribonucleotidyltransferase and cap-specific methyltransferase activities. How P interacts with L and mediates the association with the free form of N and with the ribonucleoprotein is not clear for HMPV or other major human pathogens, including the viruses that cause measles, Ebola and rabies. Here we report a cryo-electron microscopy reconstruction that shows the ring-shaped structure of the polymerase and capping domains of HMPV-L bound to a tetramer of P. The connector and methyltransferase domains of L are mobile with respect to the core. The putative priming loop that is important for the initiation of RNA synthesis is fully retracted, which leaves space in the active-site cavity for RNA elongation. P interacts extensively with the N-terminal region of L, burying more than 4,016 Å of the molecular surface area in the interface. Two of the four helices that form the coiled-coil tetramerization domain of P, and long C-terminal extensions projecting from these two helices, wrap around the L protein in a manner similar to tentacles. The structural versatility of the four P protomers-which are largely disordered in their free state-demonstrates an example of a 'folding-upon-partner-binding' mechanism for carrying out P adaptor functions. The structure shows that P has the potential to modulate multiple functions of L and these results should accelerate the design of specific antiviral drugs.

PubMed: 31698413
DOI: 10.1038/s41586-019-1759-1

実験手法

ELECTRON MICROSCOPY (3.7 Å)