TY - JOUR
T1 - Measles and Nipah virus assembly
T2 - Specific lipid binding drives matrix polymerization
AU - Norris, Michael J.
AU - Husby, Monica L.
AU - Kiosses, William B.
AU - Yin, Jieyun
AU - Saxena, Roopashi
AU - Rennick, Linda J.
AU - Heiner, Anja
AU - Harkins, Stephanie S.
AU - Pokhrel, Rudramani
AU - Schendel, Sharon L.
AU - Hastie, Kathryn M.
AU - Landeras-Bueno, Sara
AU - Salie, Zhe Li
AU - Lee, Benhur
AU - Chapagain, Prem P.
AU - Maisner, Andrea
AU - Paul Duprex, W.
AU - Stahelin, Robert V.
AU - Saphire, Erica Ollmann
N1 - Funding Information:
We gratefully acknowledge K. Fuller and T. Alkutkar for technical assistance. Data for the NiV-M structure were collected on beamline 12-2 of the Stanford Synchrotron Radiation Lightsource. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy (DOE), Office of Science, and Office of Basic Energy Sciences under contract no. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the National Institutes of Health (NIH) and National Institute of General Medical Sciences (P30GM133894). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH. Data for the NiV-M + C8-PI(4,5)P2 structure were collected on beamlines 23-ID-B of the Advanced Photon Source, a U.S. DOE Office of Science user facility operated for the DOE Office of Science by Argonne National Laboratory under contract no. DE-AC02-06CH11357. Data for the MeV-M structure were obtained through use of the Lilly Research Laboratories Collaborative Access Team (LRL-CAT) beamline at Sector 31 of the Advanced Photon Source provided by Eli Lilly Company, which operates the facility. The La Jolla Institute Zeiss LSM 880 was acquired through the Shared Instrumentation Grant Program (S10): NIH S10OD021831.This work was supported by institutional funds of the La Jolla Institute for Immunology (to E.O.S.); NIH/NIAID AI081077 and NIH S10OD027043 (to R.V.S.); the Henry L. Hillman Foundation (to W.P.D.); the Deutsche Forschungsgemeinschaft (German Research Foundation, Projektnummer 197785619 - SFB 1021) (to A.M.); and NIH/NIAID AI125536 AI123449 (to B.L.).
Publisher Copyright:
© 2022 The Authors, some rights reserved
PY - 2022/7
Y1 - 2022/7
N2 - Measles virus, Nipah virus, and multiple other paramyxoviruses cause disease outbreaks in humans and animals worldwide. The paramyxovirus matrix (M) protein mediates virion assembly and budding from host cell membranes. M is thus a key target for antivirals, but few high-resolution structures of paramyxovirus M are available, and we lack the clear understanding of how viral M proteins interact with membrane lipids to mediate viral assembly and egress that is needed to guide antiviral design. Here, we reveal that M proteins associate with phosphatidylserine and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] at the plasma membrane. Using x-ray crystallography, electron microscopy, and molecular dynamics, we demonstrate that PI(4,5)P2 binding induces conformational and electrostatic changes in the M protein surface that trigger membrane deformation, matrix layer polymerization, and virion assembly.
AB - Measles virus, Nipah virus, and multiple other paramyxoviruses cause disease outbreaks in humans and animals worldwide. The paramyxovirus matrix (M) protein mediates virion assembly and budding from host cell membranes. M is thus a key target for antivirals, but few high-resolution structures of paramyxovirus M are available, and we lack the clear understanding of how viral M proteins interact with membrane lipids to mediate viral assembly and egress that is needed to guide antiviral design. Here, we reveal that M proteins associate with phosphatidylserine and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] at the plasma membrane. Using x-ray crystallography, electron microscopy, and molecular dynamics, we demonstrate that PI(4,5)P2 binding induces conformational and electrostatic changes in the M protein surface that trigger membrane deformation, matrix layer polymerization, and virion assembly.
UR - http://www.scopus.com/inward/record.url?scp=85134780857&partnerID=8YFLogxK
U2 - 10.1126/sciadv.abn1440
DO - 10.1126/sciadv.abn1440
M3 - Article
C2 - 35857835
AN - SCOPUS:85134780857
SN - 2375-2548
VL - 8
JO - Science advances
JF - Science advances
IS - 29
M1 - eabn1440
ER -