LitCovid-sentences  

PMC:7094172 / 4762-10117 JSONTXT 14 Projects

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Id Subject Object Predicate Lexical cue
T31 0-60 Sentence denotes Structure of the N-Terminal Domain of the MERS-CoV N Protein
T32 61-192 Sentence denotes We determined the crystal structure of MERS-CoV N-NTD by molecular replacement (MR) using the structure of HCoV-OC43 N-NTD (PDB ID:
T33 193-352 Sentence denotes 4J3K) as the search model.24 The final structure was refined to R-factor and R-free values of 0.26 and 0.29, respectively, at a resolution of 2.6 Å (Table S1).
T34 353-506 Sentence denotes Each asymmetric unit contained four N-NTD molecules assembled into two identical dimers with an overall RMSD of 0.28 Å between the dimers (Figure S1A,B).
T35 507-596 Sentence denotes The monomers shared a similar structural core preceded by a flexible region (Figure S1D).
T36 597-888 Sentence denotes The core consisted of a five-stranded antiparallel β-sheet sandwiched between loops arranged in a right-handed, fist-shaped structure conserved among the CoVs.25 In our structure, however, the loop connecting strands β2 and β3 protruding out of the core into other CoV N proteins was absent.
T37 889-993 Sentence denotes Unlike the reported structures that have a monomeric conformation, our structure was atypically dimeric.
T38 994-1074 Sentence denotes Figure 1B shows the details of the interactions in the MERS-CoV N protein dimer.
T39 1075-1130 Sentence denotes We named the units monomer 1 and monomer 2 (Figure 1A).
T40 1131-1361 Sentence denotes According to the amino acid composition of the binding site on monomer 2, we divided the dimeric interface into two areas: one located on the N-terminus flexible region and the other on the loop between β4 and β5 of the N protein.
T41 1362-1569 Sentence denotes In the first area, W43, N66, N68, Y102, and F135 of monomer 1 generated a conserved hydrophobic pocket permitting the side chain of M38 of monomer 2 to enter this hole by a hydrophobic contact (Figure 1C,D).
T42 1570-1703 Sentence denotes H37 and N39 of monomer 2 were packed against W43 and F135 of monomer 1, respectively, and contributed to the hydrophobic interaction.
T43 1704-1823 Sentence denotes The side chains of N39 of monomer 2 formed one hydrogen bond with the N68 backbone in monomer 1 at a distance of 2.6 Å.
T44 1824-1872 Sentence denotes The second area was relatively more hydrophilic.
T45 1873-2061 Sentence denotes The main chain oxygens of G104, F135, and T137 of monomer 2 formed three hydrogen bonds with the side chains of Q73 and T134 of monomer 1 at distances of 3.8, 3.2, and 3.7 Å, respectively.
T46 2062-2192 Sentence denotes The side chain of N139 on monomer 2 formed a hydrogen bond with the main chain oxygen of T137 on monomer 1 at a distance of 3.6 Å.
T47 2193-2308 Sentence denotes The interactions of the first and second areas comprise buried surface areas (BSA) of 289 and 103 Å2, respectively.
T48 2309-2456 Sentence denotes The small surface area buried at the interface accounts for ∼5 kcal mol–1 binding energy,26 which translates to a dissociation constant of ∼200 mM.
T49 2457-2605 Sentence denotes Thus, the dimer described here is unique in that it is non-native and relies on vector-fusion residues (H37 and M38) to maintain its dimeric status.
T50 2606-2898 Sentence denotes This property may also explain why the present structure has an oligomeric status different from previously reported structures for the CoV N protein.24,27−30 We used cross-linking experiments to analyze the oligomeric capacity of MERS N-NTD containing the vector-fusion residues in solution.
T51 2899-2949 Sentence denotes MERS N-NTD had a dimeric conformation in solution.
T52 2950-3134 Sentence denotes Our structure indicated that W43 played an essential role in forming the hydrophobic pocket accommodating the vector-fusion residues and, therefore, mediated the N-NTD dimer formation.
T53 3135-3221 Sentence denotes The W43A mutation significantly reduced the oligomeric tendency of N-NTD (Figure S1C).
T54 3222-3352 Sentence denotes This further supports that the “exogenous residues” encoded by the vector backbone mediated the formation of the non-native dimer.
T55 3353-3435 Sentence denotes We also superimposed the previously published structure of MERS-CoV N-NTD (PDB ID:
T56 3436-3516 Sentence denotes 4ud1)27 containing a native N-terminal flexible region with our dimer structure.
T57 3517-3662 Sentence denotes The side chain of N38 in the native structure could not interact with the hydrophobic pocket as the former is hydrophilic and short (Figure S1E).
T58 3663-3808 Sentence denotes Thus, it may be possible to utilize small compounds to replace the vector-fusion residues and stabilize the PPI through hydrophobic interactions.
T59 3809-4007 Sentence denotes Figure 1 Structure and sequence of MERS-CoV N-NTD. (A) Overall structure of the MERS-CoV N-NTD dimer containing monomers 1 and 2 is depicted as a cartoon and colored yellow and green, respectively.
T60 4008-4125 Sentence denotes Residues involved in dimerization are shown as sticks and highlighted in (B). (B) Interactions among MERS-CoV N-NTDs.
T61 4126-4323 Sentence denotes Dimerization is mediated mainly by vector-fusion residues interacting with the conserved hydrophobic regions on the core structure (first area) along with the residues surrounding it (second area).
T62 4324-4409 Sentence denotes Interacting residues on monomers 1 and 2 are labeled in black and blue, respectively.
T63 4410-4497 Sentence denotes Vector-fusion and conserved hydrophobic regions are colored cyan and red, respectively.
T64 4498-4586 Sentence denotes The color of all other interacting residues is the same as that for each monomer in (A).
T65 4587-4717 Sentence denotes Polar contacts are indicated with red dashed lines. (C) Upper panel: close-up of the interacting region of vector-fusion residues.
T66 4718-4803 Sentence denotes The surface was colored according to the hydrophobicity level at the protein surface.
T67 4804-4891 Sentence denotes Vector-fusion residues (black) are shown as sticks to emphasize the hydrophobic pocket.
T68 4892-4904 Sentence denotes Lower panel:
T69 4905-4998 Sentence denotes 2D diagrams of the interaction between the hydrophobic pocket and the vector-fusion residues.
T70 4999-5031 Sentence denotes The latter are labeled in black.
T71 5032-5170 Sentence denotes The hydrophobic contacts are indicated with black dashed lines. (D) Sequence alignment of various CoV N proteins in the N-terminal region.
T72 5171-5220 Sentence denotes Red letters indicate strictly conserved residues.
T73 5221-5268 Sentence denotes Cyan indicates conservative substitution sites.
T74 5269-5355 Sentence denotes Hydrophobic regions involved in unusual dimerization are indicated by black triangles.