气候变化领域集成服务门户(CCPortal): Immature HIV-1 assembles from Gag dimers leaving partial hexamers at lattice edges as potential substrates for proteolytic maturation

CCPortal

DOI	10.1073/pnas.2020054118
	Immature HIV-1 assembles from Gag dimers leaving partial hexamers at lattice edges as potential substrates for proteolytic maturation
	Tan A.; Pak A.J.; Morado D.R.; Voth G.A.; Briggs J.A.G.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	The CA (capsid) domain of immature HIV-1 Gag and the adjacent spacer peptide 1 (SP1) play a key role in viral assembly by forming a lattice of CA hexamers, which adapts to viral envelope curvature by incorporating small lattice defects and a large gap at the site of budding. This lattice is stabilized by intrahexameric and interhexameric CA-CA interactions, which are important in regulating viral assembly and maturation. We applied subtomogram averaging and classification to determine the oligomerization state of CA at lattice edges and found that CA forms partial hexamers. These structures reveal the network of interactions formed by CA-SP1 at the lattice edge. We also performed atomistic molecular dynamics simulations of CA-CA interactions stabilizing the immature lattice and partial CA-SP1 helical bundles. Free energy calculations reveal increased propensity for helix-to-coil transitions in partial hexamers compared to complete six-helix bundles. Taken together, these results suggest that the CA dimer is the basic unit of lattice assembly, partial hexamers exist at lattice edges, these are in a helix-coil dynamic equilibrium, and partial helical bundles are more likely to unfold, representing potential sites for HIV-1 maturation initiation. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	HIV-1 \| cryo-electron tomography \| molecular dynamics simulations \| virus assembly \| maturation
语种	英语
scopus关键词	Gag protein; spacer peptide 1; unclassified drug; viral protein; virus capsid antigen; Article; energy metabolism; Human immunodeficiency virus 1; immature virus; molecular dynamics; oligomerization; priority journal; protein degradation; protein processing; protein protein interaction; virus assembly
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181000
作者单位	Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, CB2 0QH, United Kingdom; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, 69117, Germany; Department of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, Chicago, IL 60637, United States; James Franck Institute, University of Chicago, Chicago, IL 60637, United States
推荐引用方式 GB/T 7714	Tan A.,Pak A.J.,Morado D.R.,et al. Immature HIV-1 assembles from Gag dimers leaving partial hexamers at lattice edges as potential substrates for proteolytic maturation[J],2021,118(3).
APA	Tan A.,Pak A.J.,Morado D.R.,Voth G.A.,&Briggs J.A.G..(2021).Immature HIV-1 assembles from Gag dimers leaving partial hexamers at lattice edges as potential substrates for proteolytic maturation.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Tan A.,et al."Immature HIV-1 assembles from Gag dimers leaving partial hexamers at lattice edges as potential substrates for proteolytic maturation".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).