About: Influence of hydrophobic and electrostatic residues on SARS-coronavirus S2 protein stability: Insights into mechanisms of general viral fusion and inhibitor design

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About: Influence of hydrophobic and electrostatic residues on SARS-coronavirus S2 protein stability: Insights into mechanisms of general viral fusion and inhibitor design Goto Sponge NotDistinct Permalink

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	Influence of hydrophobic and electrostatic residues on SARS-coronavirus S2 protein stability: Insights into mechanisms of general viral fusion and inhibitor design
Creator	Al-Khooly, Dina Aydin, Halil Lee, Jeffrey
Source	Medline; PMC
abstract	Severe acute respiratory syndrome (SARS) is an acute respiratory disease caused by the SARS-coronavirus (SARS-CoV). SARS-CoV entry is facilitated by the spike protein (S), which consists of an N-terminal domain (S1) responsible for cellular attachment and a C-terminal domain (S2) that mediates viral and host cell membrane fusion. The SARS-CoV S2 is a potential drug target, as peptidomimetics against S2 act as potent fusion inhibitors. In this study, site-directed mutagenesis and thermal stability experiments on electrostatic, hydrophobic, and polar residues to dissect their roles in stabilizing the S2 postfusion conformation was performed. It was shown that unlike the pH-independent retroviral fusion proteins, SARS-CoV S2 is stable over a wide pH range, supporting its ability to fuse at both the plasma membrane and endosome. A comprehensive SARS-CoV S2 analysis showed that specific hydrophobic positions at the C-terminal end of the HR2, rather than electrostatics are critical for fusion protein stabilization. Disruption of the conserved C-terminal hydrophobic residues destabilized the fusion core and reduced the melting temperature by 30°C. The importance of the C-terminal hydrophobic residues led us to identify a 42-residue substructure on the central core that is structurally conserved in all existing CoV S2 fusion proteins (root mean squared deviation = 0.4 Å). This is the first study to identify such a conserved substructure and likely represents a common foundation to facilitate viral fusion. We have discussed the role of key residues in the design of fusion inhibitors and the potential of the substructure as a general target for the development of novel therapeutics against CoV infections.
has issue date	2014-03-19(xsd:dateTime)
bibo:doi	10.1002/pro.2442
bibo:pmid	24519901
has license	bronze-oa
sha1sum (hex)	d8e866953830006644dc382a23b20fb5c69cd1a4
schema:url	https://doi.org/10.1002/pro.2442
resource representing a document's title	Influence of hydrophobic and electrostatic residues on SARS-coronavirus S2 protein stability: Insights into mechanisms of general viral fusion and inhibitor design
has PubMed Central identifier	PMC4005712
has PubMed identifier	24519901
schema:publication	Protein Science
resource representing a document's body	covid:d8e866953830006644dc382a23b20fb5c69cd1a4#body_text
is schema:about of	named entity 'general' named entity 'critical' named entity 'existing' named entity 'hydrophobic' named entity 'experiments' named entity 'mediates' named entity 'specific' named entity 'residues' named entity 'ELECTROSTATICS' named entity 'CELLULAR' named entity 'REDUCED' named entity 'DRUG TARGET' named entity 'INFECTIONS' named entity 'STABILIZING' named entity 'MEDIATES' named entity 'PROTEIN ' named entity 'PLASMA MEMBRANE' named entity 'CORONAVIRUS' covid:arg/d8e866953830006644dc382a23b20fb5c69cd1a4 named entity 'SARS-CoV' named entity 'SARS-CoV' named entity 'C-terminal' named entity 'Disruption' named entity 'led' named entity 'hydrophobic' named entity 'spike' named entity 'inhibitors' named entity 'conserved' named entity 'residues' named entity 'C-terminal' named entity 'electrostatic' named entity 'drug target' named entity 'mechanisms' named entity 'C-terminal' named entity 'hydrophobic residues' named entity 'peptidomimetics' named entity 'coronavirus' named entity 'drug target' named entity 'cell membrane' named entity 'SARS' named entity 'melting temperature' named entity 'plasma membrane' named entity 'postfusion' named entity 'site-directed mutagenesis' named entity 'fusion proteins' named entity 'fusion inhibitors' named entity 'N-terminal domain' named entity 'respiratory disease' named entity 'coronavirus' named entity 'electrostatic' named entity 'viral' named entity 'protein' named entity 'heptad repeat' named entity 'SARS-CoV' named entity 'CoV' named entity 'SARS-CoV' named entity 'hydrophobic residues' named entity 'free energy' named entity '5.0' named entity 'hydrophobic residues' named entity 'ASLV' named entity 'SARS-CoV' named entity 'coronaviruses' named entity 'coronavirus' named entity 'fusion core' named entity 'HR2' named entity 'SARS-CoV' named entity 'plasma membrane' named entity 'SARS-CoV' named entity 'SARS-CoV' named entity 'proteolytically cleaved' named entity 'w/v' named entity 'SARS-CoV' named entity 'postfusion' named entity 'viruses' named entity 'postfusion' named entity 'N-terminal' named entity 'isoleucine' named entity 'previously identified'

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