About: Glycine 29 Is Critical for Conformational Changes of the Spike Glycoprotein of Mouse Hepatitis Virus A59 Triggered by either Receptor Binding or High pH

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About: Glycine 29 Is Critical for Conformational Changes of the Spike Glycoprotein of Mouse Hepatitis Virus A59 Triggered by either Receptor Binding or High pH Goto Sponge NotDistinct Permalink

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Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Glycine 29 Is Critical for Conformational Changes of the Spike Glycoprotein of Mouse Hepatitis Virus A59 Triggered by either Receptor Binding or High pH
Creator	Liu, Yan Liu, Peng Peng, Guiqing Li, Fang Qian, Zhaohui Li, Pei Mu, Zhixia Ou, Xiuyuan Mi, Dan Guo, Ruixuan Holmes, Kathryn Li, Mu Li, Ou
topic	covid:acee92aa1bfa77bcb9516cbed2ef86751d5bcab5#this
Source	Medline; PMC
abstract	Mouse hepatitis virus (MHV) uses its N-terminal domain (NTD) of the viral spike (S) protein to bind the host receptor mouse carcinoembryonic antigen-related cell adhesion molecule 1a (mCEACAM1a) and mediate virus entry. Our previous crystal structure study of the MHV NTD/mCEACAM1a complex (G. Peng, D. Sun, K. R. Rajashankar, Z. Qian, et al., Proc Natl Acad Sci U S A 108:10696–10701, 2011, https://doi.org/10.1073/pnas.1104306108) reveals that there are 14 residues in the NTD interacting with the receptor. However, their contribution to receptor binding and virus entry has not been fully investigated. Here we analyzed 13 out of 14 contact residues by mutagenesis and identified I22 as being essential for receptor binding and virus entry. Unexpectedly, we found that G29 was critical for the conformational changes of the S protein triggered by either receptor binding or high pH. Replacement of G29 with A, D, F, K, M, and T, to different extents, caused spontaneous dissociation of S1 from the S protein, resulting in an enhancement of high-pH-triggered receptor-independent syncytium (RIS) formation in HEK293T cells, compared to the wild type (WT). In contrast, replacement of G29 with P, a turn-prone residue with a strict conformation, hindered virus entry and conformational changes of the S protein triggered by either receptor binding or pH 8.0, suggesting that the structural turn around G29 and its flexibility are critical. Finally, stabilization of the NTD by G29P had almost no effect on pH-independent RIS induced by the Y320A mutation in the C-terminal domain (CTD) of the S1 subunit, indicating that there might be an absence of cross talk between the NTD and CTD during conformational changes of the S protein. Our study will aid in better understanding the mechanism of how conformational changes of the S protein are triggered. IMPORTANCE Binding of the MHV S protein to the receptor mCEACAM1a triggers conformational changes of S proteins, leading to the formation of a six-helix bundle and viral and cellular membrane fusion. However, the mechanism by which the conformational change of the S protein is initiated after receptor binding has not been determined. In this study, we showed that while replacement of G29, a residue at the edge of the receptor binding interface and the center of the structural turn after the β1-sheet of the S protein, with D or T triggered spontaneous conformational changes of the S protein and pH-independent RIS, the G29P mutation significantly impeded the conformational changes of S proteins triggered by either receptor binding or pH 8.0. We reason that this structural turn might be critical for conformational changes of the S protein and that altering this structural turn could initiate conformational changes of the S protein, leading to membrane fusion.
has issue date	2019-08-02(xsd:dateTime)
bibo:doi	10.1128/jvi.01046-19
bibo:pmid	31375571
has license	bronze-oa
sha1sum (hex)	acee92aa1bfa77bcb9516cbed2ef86751d5bcab5
schema:url	https://doi.org/10.1128/jvi.01046-19
resource representing a document's title	Glycine 29 Is Critical for Conformational Changes of the Spike Glycoprotein of Mouse Hepatitis Virus A59 Triggered by either Receptor Binding or High pH
has PubMed Central identifier	PMC6798120
has PubMed identifier	31375571
schema:publication	Journal of Virology
resource representing a document's body	covid:acee92aa1bfa77bcb9516cbed2ef86751d5bcab5#body_text
is http://vocab.deri.ie/void#inDataset of	proxy:http/ns.inria.fr/covid19/acee92aa1bfa77bcb9516cbed2ef86751d5bcab5
is schema:about of	named entity 'protein' named entity 'binding' named entity 'receptor' named entity 'compared' named entity 'proteins' named entity 'CTD' named entity 'cell adhesion molecule' named entity 'viral' named entity 'arginine' named entity 'receptor' named entity 'MHV' named entity 'diseases' named entity 'receptor' named entity 'isoleucine' named entity 'receptor' named entity 'indicating' named entity 'protein' named entity 'critical' named entity 'critical' named entity 'bind' named entity 'Here' named entity 'HERE' named entity 'VIRUS ENTRY' named entity 'BUNDLE' named entity 'DIFFERENT' named entity 'PROTEIN BINDING' named entity 'REPLACEMENT' named entity 'EITHER' named entity 'ISOLEUCINE' named entity 'ORG' named entity 'PROTEINS' named entity 'EXTENTS' named entity 'S PROTEIN' named entity 'mutation' named entity 'receptor' named entity 'critical' named entity 'MHV' named entity 'fusion' named entity 'protein' named entity 'receptor' named entity 'contact' named entity 'hepatic' named entity 'Phylogenetically' named entity 'C-terminal domain' named entity 'triggered' named entity 'virus' named entity 'alleles' named entity 'conformational' named entity 'tumorigenesis' named entity 'neurotropic' named entity 'protein' named entity 'Replacement' named entity 'complex' named entity 'induced' named entity 'subunit' named entity 'crystal structure' named entity 'RIS' named entity 'member' named entity 'leading' named entity 'Ig-like' named entity '2011' named entity 'flexibility' named entity 'formation' named entity 'Sun' named entity 'IgSF' named entity 'residues' named entity 'cells'

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