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 - 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 -