PMC:7094172 / 15213-17853 JSONTXT 14 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T120 0-145 Sentence denotes The presence of multiple intrinsically disordered regions in the N protein precluded the determination of its structure by X-ray crystallography.
T121 146-295 Sentence denotes Instead, we used rigid body modeling of the SAXS data with the N-terminal domain (NTD; solved in this study) and the C-terminal domains (CTD, PDB ID:
T122 296-409 Sentence denotes 6G13).23 In this way, we obtained structural models for the free N protein and its complex with P3 (Figure 3B,C).
T123 410-439 Sentence denotes Excellent fits were obtained.
T124 440-560 Sentence denotes Representative structural models for the full-length protein without and with P3 are shown in Figure 3D,E, respectively.
T125 561-662 Sentence denotes The free N protein formed a tetramer through CTD with the NTD freely hanging in solution (Figure 3D).
T126 663-863 Sentence denotes The conformation of the solution was consistent with structures previously reported for other CoV N proteins.33 The N-P3 complex formed a compact hexadecamer with a sunburst configuration (Figure 3E).
T127 864-962 Sentence denotes The CTDs formed a central ring and non-native NTD dimers formed “spikes” protruding from the ring.
T128 963-1135 Sentence denotes Consistent with ligand-induced aggregation, we observed a “blue shift” in the fluorescence spectrum of the full-length MERS-CoV N protein in the presence of P3 (Figure 3F).
T129 1136-1338 Sentence denotes The addition of P3 also delayed N protein thermal denaturation and changed the shape of the denaturation curve, further suggesting that large protein aggregates formed in the presence of P3 (Figure 3G).
T130 1339-1414 Sentence denotes The structure explains how N-NTD dimerization decreased MERS-CoV viability.
T131 1415-1475 Sentence denotes The N protein packages the viral genome into an RNP complex.
T132 1476-1735 Sentence denotes Several models for N-CTD dimer assembly have been proposed for the formation of filamentous RNPs.33 All of the proposed interfaces between N-CTD dimers occurred on the side-faces of the CTD cuboid perpendicular to the proposed RNA-binding surface (Figure 3H).
T133 1736-2027 Sentence denotes Combinatorial use of any region on the side-faces of the CTD dimer cuboid may facilitate manipulation of the RNP length and curvature without obstructing the RNA-binding surface.28,34 However, the SAXS results indicated that N-CTD aggregation occurred on the β-sheet floor of the CTD cuboid.
T134 2028-2214 Sentence denotes For this reason, the RNA-binding surface of the CTD is occluded by the neighboring CTD on the ring and by the non-native NTD dimer making direct contact with the CTD (Figures 3H and S3).
T135 2215-2398 Sentence denotes In addition, the CTD cuboids in the aggregation naturally form a topologically closed octamer, leaving no open ends for further addition of CTD cuboids to form a long filamentous RNP.
T136 2399-2556 Sentence denotes Both the loss of the RNA-binding surface and the inability to incorporate further N protein molecules beyond an octamer may inhibit the formation of the RNP.
T137 2557-2640 Sentence denotes Therefore, P3 may inhibit MERS-CoV RNP formation by inducing N protein aggregation.