Crystal Structure of the Rabies Virus Nucleoprotein-RNA Complex

Albertini, Aurélie A.; Wernimont, A.K.; Muzioł, Tadeusz; Ravelli, R.B.G.; Clapier, Cedric R.; Schoehn, Guy; Weissenhorn, Winfríed; Ruigrok, Rob W.H.

doi:10.1126/science.1125280

Cited by 296 publications

(304 citation statements)

References 22 publications

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“…54 The N-terminal domain is likely shared among Mononegavirales. Known 3D structures of NP from several virus families [77][78][79][80][81] in this order possess the same topology ( Fig. 3A-D).…”

Section: The Zinc-finger Domain Of Vp30mentioning

confidence: 88%

Predictive and comparative analysis of Ebolavirus proteins

2015

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Ebolavirus is the pathogen for Ebola Hemorrhagic Fever (EHF). This disease exhibits a high fatality rate and has recently reached a historically epidemic proportion in West Africa. Out of the 5 known Ebolavirus species, only Reston ebolavirus has lost human pathogenicity, while retaining the ability to cause EHF in long-tailed macaque. Significant efforts have been spent to determine the three-dimensional (3D) structures of Ebolavirus proteins, to study their interaction with host proteins, and to identify the functional motifs in these viral proteins. Here, in light of these experimental results, we apply computational analysis to predict the 3D structures and functional sites for Ebolavirus protein domains with unknown structure, including a zinc-finger domain of VP30, the RNA-dependent RNA polymerase catalytic domain and a methyltransferase domain of protein L. In addition, we compare sequences of proteins that interact with Ebolavirus proteins from RESTV-resistant primates with those from RESTV-susceptible monkeys. The host proteins that interact with GP and VP35 show an elevated level of sequence divergence between the RESTV-resistant and RESTV-susceptible species, suggesting that they may be responsible for host specificity. Meanwhile, we detect variable positions in protein sequences that are likely associated with the loss of human pathogenicity in RESTV, map them onto the 3D structures and compare their positions to known functional sites. VP35 and VP30 are significantly enriched in these potential pathogenicity determinants and the clustering of such positions on the surfaces of VP35 and GP suggests possible uncharacterized interaction sites with host proteins that contribute to the virulence of Ebolavirus.

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Section: The Zinc-finger Domain Of Vp30mentioning

confidence: 88%

Predictive and comparative analysis of Ebolavirus proteins

2015

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“…In the case of VSV, almost 80% of the rings contain 10 protomers of N 3 , suggesting that the decamer is their low energy form. The atomic structure of this artificially constrained arrangement was solved by X-ray crystallography 2 and provided insights into the structure of the nucleoprotein subunit, the nature of inter-subunit interactions, the mechanism of genome sequestering and the necessity of conformational rearrangements in the nucleoprotein required for access of the viral polymerase into the RNA-binding cleft 2,4 . For the second question, cryo-electron microscopy (cryoEM) analysis of the entire virion recently culminated in a 10 Å resolution threedimensional (3D) reconstruction of the skeleton trunk, where the viral matrix protein M, which role in the nucleocapsid condensation has been under debate since 30 years [5][6][7][8] , bridges consecutive turns of the N-RNA helix 1 .…”

Section: Esicular Stomatitis Virus (Vsv) a Representative Of Thementioning

confidence: 99%

Self-organization of the vesicular stomatitis virus nucleocapsid into a bullet shape

et al. 2013

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The typical bullet shape of Rhabdoviruses is thought to rely on the matrix protein for stabilizing the nucleocapsid coil. Here we scrutinize the morphology of purified and recombinant nucleocapsids of vesicular stomatitis virus in vitro. We elucidate pH and ionic strength conditions for their folding into conical tips and further growth into whole bullets, and provide cryo-electron microscopy reconstructions of the bullet tip and the helical trunk. We address conformational variability of the reconstituted nucleocapsids and the issue of constraints imposed by the binding of matrix protein. Our findings bridge the gap between the isolated nucleoprotein-RNA string in its form of an undulating ribbon, and the tight bullet-shaped virion skeleton.

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“…For some of these, ribonucleoprotein (RNP) complexes have been visualized by crystallography or electron microscopy (FLUA) (18), (RABV) (14), (HRSV) (15), (VSV) (16). The crystallized RNP oligomers are high-order ring structures formed by specific contacts of loops or chain termini of neighboring N subunits.…”

mentioning

confidence: 99%

“…Structures are available for N from several negative-sense RNA viruses, including influenza A virus (FLUA) (13), rabies virus (RABV) (14), human respiratory syncytial virus (HRSV) (15), vesicular stomatitis virus (VSV) (16), and Borna disease virus (BDV) (17). For some of these, ribonucleoprotein (RNP) complexes have been visualized by crystallography or electron microscopy (FLUA) (18), (RABV) (14), (HRSV) (15), (VSV) (16).…”

mentioning

confidence: 99%

Structure of the Rift Valley fever virus nucleocapsid protein reveals another architecture for RNA encapsidation

Raymond¹,

Piper²,

Gerrard

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

117

146

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Rift Valley fever virus (RVFV) is a negative-sense RNA virus (genus Phlebovirus, family Bunyaviridae) that infects livestock and humans and is endemic to sub-Saharan Africa. Like all negative-sense viruses, the segmented RNA genome of RVFV is encapsidated by a nucleocapsid protein (N). The 1.93-Å crystal structure of RVFV N and electron micrographs of ribonucleoprotein (RNP) reveal an encapsidated genome of substantially different organization than in other negative-sense RNA virus families. The RNP polymer, viewed in electron micrographs of both virus RNP and RNP reconstituted from purified N with a defined RNA, has an extended structure without helical symmetry. N-RNA species of ∼100-kDa apparent molecular weight and heterogeneous composition were obtained by exhaustive ribonuclease treatment of virus RNP, by recombinant expression of N, and by reconstitution from purified N and an RNA oligomer. RNA-free N, obtained by denaturation and refolding, has a novel all-helical fold that is compact and well ordered at both the N and C termini. Unlike N of other negative-sense RNA viruses, RVFV N has no positively charged surface cleft for RNA binding and no protruding termini or loops to stabilize a defined N-RNA oligomer or RNP helix. A potential protein interaction site was identified in a conserved hydrophobic pocket. The nonhelical appearance of phlebovirus RNP, the heterogeneous ∼100-kDa N-RNA multimer, and the N fold differ substantially from the RNP and N of other negative-sense RNA virus families and provide valuable insights into the structure of the encapsidated phlebovirus genome.ribonucleoprotein | viral protein | segmented genome | negative-sense RNA virus

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Crystal Structure of the Rabies Virus Nucleoprotein-RNA Complex

Cited by 296 publications

References 22 publications

Predictive and comparative analysis of Ebolavirus proteins

Predictive and comparative analysis of Ebolavirus proteins

Self-organization of the vesicular stomatitis virus nucleocapsid into a bullet shape

Structure of the Rift Valley fever virus nucleocapsid protein reveals another architecture for RNA encapsidation

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