About: Structure-Based Design of Prefusion-Stabilized Filovirus Glycoprotein Trimers

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An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Structure-Based Design of Prefusion-Stabilized Filovirus Glycoprotein Trimers
Creator	Blokland, Sven Rutten, Lucy Mclellan, Jason Gilman, Morgan Juraszek, Jarek Langedijk Correspondence, Johannes
Source	Elsevier; Medline; PMC
abstract	Ebola virus causes severe hemorrhagic fever, often leading to death in humans. The trimeric fusion glycoprotein (GP) is the sole target for neutralizing antibodies and is the major focus of vaccine development. Soluble GP ectodomains are unstable and mostly monomeric when not fused to a heterologous trimerization domain. Here, we report structure-based designs of Ebola and Marburg GP trimers based on a stabilizing mutation in the hinge loop in refolding region 1 and substitution of a partially buried charge at the interface of the GP1 and GP2 subunits. The combined substitutions (T577P and K588F) substantially increased trimer expression for Ebola GP proteins. We determined the crystal structure of stabilized GP from the Makona Zaire ebolavirus strain without a trimerization domain or complexed ligand. The structure reveals that the stabilized GP adopts the same trimeric prefusion conformation, provides insight into triggering of GP conformational changes, and should inform future filovirus vaccine development.
has issue date	2020-03-31(xsd:dateTime)
bibo:doi	10.1016/j.celrep.2020.03.025
bibo:pmid	32234486
has license	no-cc
sha1sum (hex)	651d3cd95998b7221345e6369aed91ad13eb2a22
schema:url	https://doi.org/10.1016/j.celrep.2020.03.025
resource representing a document's title	Structure-Based Design of Prefusion-Stabilized Filovirus Glycoprotein Trimers
has PubMed Central identifier	PMC7118701
has PubMed identifier	32234486
schema:publication	Cell Rep
resource representing a document's body	covid:651d3cd95998b7221345e6369aed91ad13eb2a22#body_text
is schema:about of	named entity 'stabilizing' named entity 'CC BY-NC-ND' named entity 'complexed' named entity 'March' named entity 'trimer' named entity 'structure' named entity 'Highlights' named entity 'proteins' named entity 'severe' named entity 'stabilizing' named entity 'Structure-Based Design' named entity 'USEFUL' named entity 'TRIGGERING' named entity 'FUSED TO' named entity 'NOT FUSED' named entity 'COMBINED' named entity 'STABILIZED' named entity 'HINGE' named entity 'STRAIN' named entity 'EXPRESSION' named entity 'CONFORMATION' named entity 'CAUSES' named entity 'NC-' named entity 'STRUCTURE' named entity 'LIGAND' named entity 'MAJOR' named entity 'FOCUS' named entity 'STABILIZING' named entity 'SEVERE' named entity 'FILOVIRUS' named entity 'MARCH' named entity 'HEMORRHAGIC FEVER' named entity 'HELIX' named entity 'REPORT' named entity 'UNDERSTANDING' named entity 'EBOLA VIRUS' named entity 'SOLUBLE' named entity 'SUBSTITUTION' covid:arg/651d3cd95998b7221345e6369aed91ad13eb2a22 named entity 'OPEN' named entity '28S' named entity '30%' named entity '4540' named entity 'MECHANISMS' named entity 'DETERMINED' named entity 'LEADING' named entity 'DOMAIN' named entity 'BASED' named entity 'STRUCTURE' named entity 'GP1' named entity 'INFORM' named entity 'INCREASES' named entity 'ABSTRACT' named entity 'TRAPPED' named entity 'SOLE' named entity 'AUTHOR' named entity 'INSIGHT' named entity 'MAY BE' named entity 'DEATH' named entity 'HETEROLOGOUS' named entity 'INTERFACE' named entity 'REGION 1' named entity 'FUTURE' named entity 'NEUTRALIZING ANTIBODIES' named entity 'CRYSTAL STRUCTURE' named entity 'THESE' named entity 'BASED' named entity 'ZAIRE EBOLAVIRUS' named entity 'CONFIRMS' named entity 'LICENSE' named entity 'GLYCOPROTEIN' named entity 'ACCESS' named entity 'PROTEINS' named entity 'PROVIDES' named entity 'TRIMERIZATION' named entity 'GP2'

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