scholarly journals Structure of the SARS-Unique Domain C From the Bat Coronavirus HKU4

2019 ◽  
Vol 14 (5) ◽  
pp. 1934578X1984920 ◽  
Author(s):  
Andrew J. Staup ◽  
Ivon U. De Silva ◽  
Justin T. Catt ◽  
Xuan Tan ◽  
Robert G. Hammond ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Severe Acute Respiratory Syndrome ◽  
Protein Interactions ◽  
Nonstructural Protein ◽  
Protein Protein Interactions ◽  
Bioinformatics Analyses ◽  
Unique Domain ◽  
Bat Coronavirus ◽  
Immune Interference

Coronaviruses (CoVs) that cause infections such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome phylogenetically originate from bat CoVs. The coronaviral nonstructural protein 3 (nsp3) has been implicated in viral replication, polyprotein cleavage, and host immune interference. We report the structure of the C domain from the SARS-Unique Domain of bat CoV HKU4. The protein has a frataxin fold, consisting of 5 antiparallel β strands packed against 2 α helices. Bioinformatics analyses and nuclear magnetic resonance experiments were conducted to investigate the function of HKU4 C. The results showed that HKU4 C engages in protein-protein interactions with the nearby M domain of nsp3. The HKU4 C residues involved in protein-protein interactions are conserved in group 2c CoVs, indicating a conserved function.

scholarly journals Nuclear Magnetic Resonance Structure of the N-Terminal Domain of Nonstructural Protein 3 from the Severe Acute Respiratory Syndrome Coronavirus

2007 ◽  
Vol 81 (21) ◽  
pp. 12049-12060 ◽  
Author(s):  
Pedro Serrano ◽  
Margaret A. Johnson ◽  
Marcius S. Almeida ◽  
Reto Horst ◽  
Torsten Herrmann ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Severe Acute Respiratory Syndrome ◽  
Nonstructural Protein ◽  
Resonance Structure ◽  
Nuclear Magnetic Resonance Structure ◽  
Globular Domain ◽  
Terminal Domain ◽  
Nonstructural Protein 3 ◽  
Nuclear Magnetic

ABSTRACT This paper describes the structure determination of nsp3a, the N-terminal domain of the severe acute respiratory syndrome coronavirus (SARS-CoV) nonstructural protein 3. nsp3a exhibits a ubiquitin-like globular fold of residues 1 to 112 and a flexibly extended glutamic acid-rich domain of residues 113 to 183. In addition to the four β-strands and two α-helices that are common to ubiquitin-like folds, the globular domain of nsp3a contains two short helices representing a feature that has not previously been observed in these proteins. Nuclear magnetic resonance chemical shift perturbations showed that these unique structural elements are involved in interactions with single-stranded RNA. Structural similarities with proteins involved in various cell-signaling pathways indicate possible roles of nsp3a in viral infection and persistence.

scholarly journals Nuclear Magnetic Resonance Structure of the Nucleic Acid-Binding Domain of Severe Acute Respiratory Syndrome Coronavirus Nonstructural Protein 3

2009 ◽  
Vol 83 (24) ◽  
pp. 12998-13008 ◽  
Author(s):  
Pedro Serrano ◽  
Margaret A. Johnson ◽  
Amarnath Chatterjee ◽  
Benjamin W. Neuman ◽  
Jeremiah S. Joseph ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Nucleic Acid ◽  
Magnetic Resonance ◽  
Severe Acute Respiratory Syndrome ◽  
Binding Site ◽  
Nonstructural Protein ◽  
Globular Domain ◽  
Nucleic Acid Binding ◽  
Nonstructural Protein 3 ◽  
Nuclear Magnetic

ABSTRACT The nuclear magnetic resonance (NMR) structure of a globular domain of residues 1071 to 1178 within the previously annotated nucleic acid-binding region (NAB) of severe acute respiratory syndrome coronavirus nonstructural protein 3 (nsp3) has been determined, and N- and C-terminally adjoining polypeptide segments of 37 and 25 residues, respectively, have been shown to form flexibly extended linkers to the preceding globular domain and to the following, as yet uncharacterized domain. This extension of the structural coverage of nsp3 was obtained from NMR studies with an nsp3 construct comprising residues 1066 to 1181 [nsp3(1066-1181)] and the constructs nsp3(1066-1203) and nsp3(1035-1181). A search of the protein structure database indicates that the globular domain of the NAB represents a new fold, with a parallel four-strand β-sheet holding two α-helices of three and four turns that are oriented antiparallel to the β-strands. Two antiparallel two-strand β-sheets and two 310-helices are anchored against the surface of this barrel-like molecular core. Chemical shift changes upon the addition of single-stranded RNAs (ssRNAs) identified a group of residues that form a positively charged patch on the protein surface as the binding site responsible for the previously reported affinity for nucleic acids. This binding site is similar to the ssRNA-binding site of the sterile alpha motif domain of the Saccharomyces cerevisiae Vts1p protein, although the two proteins do not share a common globular fold.

scholarly journals Nuclear Magnetic Resonance Structure Shows that the Severe Acute Respiratory Syndrome Coronavirus-Unique Domain Contains a Macrodomain Fold

2008 ◽  
Vol 83 (4) ◽  
pp. 1823-1836 ◽  
Author(s):  
Amarnath Chatterjee ◽  
Margaret A. Johnson ◽  
Pedro Serrano ◽  
Bill Pedrini ◽  
Jeremiah S. Joseph ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Severe Acute Respiratory Syndrome ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Resonance Structure ◽  
Nuclear Magnetic Resonance Structure ◽  
Three Dimensional Structure ◽  
Unique Domain ◽  
Nuclear Magnetic

ABSTRACT The nuclear magnetic resonance (NMR) structure of a central segment of the previously annotated severe acute respiratory syndrome (SARS)-unique domain (SUD-M, for “middle of the SARS-unique domain”) in SARS coronavirus (SARS-CoV) nonstructural protein 3 (nsp3) has been determined. SUD-M(513-651) exhibits a macrodomain fold containing the nsp3 residues 528 to 648, and there is a flexibly extended N-terminal tail with the residues 513 to 527 and a C-terminal flexible tail of residues 649 to 651. As a follow-up to this initial result, we also solved the structure of a construct representing only the globular domain of residues 527 to 651 [SUD-M(527-651)]. NMR chemical shift perturbation experiments showed that SUD-M(527-651) binds single-stranded poly(A) and identified the contact area with this RNA on the protein surface, and electrophoretic mobility shift assays then confirmed that SUD-M has higher affinity for purine bases than for pyrimidine bases. In a further search for clues to the function, we found that SUD-M(527-651) has the closest three-dimensional structure homology with another domain of nsp3, the ADP-ribose-1"-phosphatase nsp3b, although the two proteins share only 5% sequence identity in the homologous sequence regions. SUD-M(527-651) also shows three-dimensional structure homology with several helicases and nucleoside triphosphate-binding proteins, but it does not contain the motifs of catalytic residues found in these structural homologues. The combined results from NMR screening of potential substrates and the structure-based homology studies now form a basis for more focused investigations on the role of the SARS-unique domain in viral infection.

scholarly journals Novel β-Barrel Fold in the Nuclear Magnetic Resonance Structure of the Replicase Nonstructural Protein 1 from the Severe Acute Respiratory Syndrome Coronavirus

2007 ◽  
Vol 81 (7) ◽  
pp. 3151-3161 ◽  
Author(s):  
Marcius S. Almeida ◽  
Margaret A. Johnson ◽  
Torsten Herrmann ◽  
Michael Geralt ◽  
Kurt Wüthrich
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Severe Acute Respiratory Syndrome ◽  
Nonstructural Protein ◽  
Resonance Structure ◽  
Nuclear Magnetic Resonance Structure ◽  
Nonstructural Protein 1 ◽  
Viral Replicase ◽  
Α Helix ◽  
Nuclear Magnetic

ABSTRACT The nonstructural protein 1 (nsp1) of the severe acute respiratory syndrome coronavirus has 179 residues and is the N-terminal cleavage product of the viral replicase polyprotein that mediates RNA replication and processing. The specific function of nsp1 is not known. Here we report the nuclear magnetic resonance structure of the nsp1 segment from residue 13 to 128, which represents a novel α/β-fold formed by a mixed parallel/antiparallel six-stranded β-barrel, an α-helix covering one opening of the barrel, and a 310-helix alongside the barrel. We further characterized the full-length 179-residue protein and show that the polypeptide segments of residues 1 to 12 and 129 to 179 are flexibly disordered. The structure is analyzed in a search for possible correlations with the recently reported activity of nsp1 in the degradation of mRNA.

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