TY - JOUR TI - Nucleocapsid assembly in pneumoviruses is regulated by conformational switching of the N protein AU - Renner, Max AU - Bertinelli, Mattia AU - Leyrat, Cédric AU - Paesen, Guido C AU - Saraiva de Oliveira, Laura Freitas AU - Huiskonen, Juha T AU - Grimes, Jonathan M A2 - Harrison, Stephen C. VL - 5 PY - 2016 DA - 2016/02/15 SP - e12627 C1 - eLife 2016;5:e12627 DO - 10.7554/eLife.12627 UR - https://doi.org/10.7554/eLife.12627 AB - Non-segmented, (-)RNA viruses cause serious human diseases. Human metapneumovirus (HMPV), an emerging pathogen of this order of viruses (Mononegavirales) is one of the main causes of respiratory tract illness in children. To help elucidate the assembly mechanism of the nucleocapsid (the viral RNA genome packaged by the nucleoprotein N) we present crystallographic structures of HMPV N in its assembled RNA-bound state and in a monomeric state, bound to the polymerase cofactor P. Our structures reveal molecular details of how P inhibits the self-assembly of N and how N transitions between the RNA-free and RNA-bound conformational state. Notably, we observe a role for the C-terminal extension of N in directly preventing premature uptake of RNA by folding into the RNA-binding cleft. Our structures suggest a common mechanism of how the growth of the nucleocapsid is orchestrated, and highlight an interaction site representing an important target for antivirals. KW - mononegavirales KW - structural virology KW - virus replication KW - pneumoviruses KW - nucleoprotein JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -