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PROSITE documentation PDOC51928

Coronavirus nucleocapsid (CoV N) protein N- and C-terminal (NTD and CTD) domains profiles





Description

Coronaviruses (CoVs) [E1] are a diverse group of enveloped, plus-stranded RNA viruses that infect humans and many animal species, in which they can cause respiratory, enteric, hepatic, central nervous system and neurological diseases of varying severity. The main CoV structural proteins are S (spike) (see <PDOC51923>), E (envelope) (see <PDOC51926>), M (membrane) (see <PDOC51927>), and N (nucleocapsid), where S, E, and M are integral membrane proteins. The N protein serves multiple purposes, such as packaging the RNA genome into helical ribonucleoproteins, modulating host cell metabolism, and regulating viral RNA synthesis during replication and transcription. The CoV N protein is a non-specific nucleic acid-binding protein. It has been shown to bind to single-stranded RNA (ssRNA), single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). The N protein binds to the viral RNA genome, forming a long helical nucleocapsid structure or ribonucleoprotein (RNP) complex. Upon infection, the N protein enters the host cell with the ribonucleoprotein core and is able to interact with a number of host proteins [1,2,3,4,5,6,7,8,9].

CoV N proteins contain two structured domains: the N-terminal domain (NTD; also called RBD), which is responsible for RNA binding, and the C-terminal domain (CTD; also called DD), which mediates oligomerization and RNA binding. The NTD and CTD form two independent domains that do not interact with each other. These domains are connected by a relatively long linker that is likely to be unstructured, and additional unstructured regions are located at the N and C termini. Together, the structured domains and unstructured regions of N protein participate in nucleic acid binding and subsequent steps of nucleocapsid formation. The N protein dimerizes via its C-terminal domain, providing a platform to recruit viral RNA; the prominent NTD is responsible for recruiting specific or non-specific RNAs; the linkers between NTD and CTD may act as a flexible arm to change the relative position of the two domains.

The CoV N NTD fold consists of a five-stranded, antiparallel β-sheet with the topology β4-β2-β3-β1-β5, partially encapsulated within extended, intertwining loops and turns connecting the β-strands (see <PDB:5N4K>). The CTD of CoV N exists in dimeric form. Each CoV N CTD monomer contains five α-helices, three 3(10) helices, and two β-strands and assumes a α14β1β2α5 topology (see <PDB:5EPW>) [5,6,7,8,9].

The profiles we developed cover the entire CoV N protein N- and C-terminal domains.

Last update:

June 2020 / First entry.

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Technical section

PROSITE methods (with tools and information) covered by this documentation:

COV_N_CTD, PS51929; Coronavirus nucleocapsid (CoV N) protein C-terminal (CTD) domain profile  (MATRIX)

COV_N_NTD, PS51928; Coronavirus nucleocapsid (CoV N) protein N-terminal (NTD) domain profile  (MATRIX)


References

1AuthorsChang C.-K. Sue S.-C. Yu T.-H. Hsieh C.-M. Tsai C.-K. Chiang Y.-C. Lee S.-J. Hsiao H.-H. Wu W.-J. Chang W.-L. Lin C.-H. Huang T.-H.
TitleModular organization of SARS coronavirus nucleocapsid protein.
SourceJ. Biomed. Sci. 13:59-72(2006).
PubMed ID16228284
DOI10.1007/s11373-005-9035-9

2AuthorsChang C.-K. Hsu Y.-L. Chang Y.-H. Chao F.-A. Wu M.-C. Huang Y.-S. Hu C.-K. Huang T.-H.
TitleMultiple nucleic acid binding sites and intrinsic disorder of severe acute respiratory syndrome coronavirus nucleocapsid protein: implications for ribonucleocapsid protein packaging.
SourceJ. Virol. 83:2255-2264(2009).
PubMed ID19052082
DOI10.1128/JVI.02001-08

3AuthorsZuwala K. Golda A. Kabala W. Burmistrz M. Zdzalik M. Nowak P. Kedracka-Krok S. Zarebski M. Dobrucki J. Florek D. Zeglen S. Wojarski J. Potempa J. Dubin G. Pyrc K.
TitleThe nucleocapsid protein of human coronavirus NL63.
SourcePLoS One. 10:E0117833-E0117833(2015).
PubMed ID25700263
DOI10.1371/journal.pone.0117833

4AuthorsSaikatendu K.S. Joseph J.S. Subramanian V. Neuman B.W. Buchmeier M.J. Stevens R.C. Kuhn P.
TitleRibonucleocapsid formation of severe acute respiratory syndrome coronavirus through molecular action of the N-terminal domain of N protein.
SourceJ. Virol. 81:3913-3921(2007).
PubMed ID17229691
DOI10.1128/JVI.02236-06

5AuthorsFan H. Ooi A. Tan Y.W. Wang S. Fang S. Liu D.X. Lescar J.
TitleThe nucleocapsid protein of coronavirus infectious bronchitis virus: crystal structure of its N-terminal domain and multimerization properties.
SourceStructure 13:1859-1868(2005).
PubMed ID16338414
DOI10.1016/j.str.2005.08.021

6AuthorsMa Y. Tong X. Xu X. Li X. Lou Z. Rao Z.
TitleStructures of the N- and C-terminal domains of MHV-A59 nucleocapsid protein corroborate a conserved RNA-protein binding mechanism in coronavirus.
SourceProtein. Cell. 1:688-697(2010).
PubMed ID21203940
DOI10.1007/s13238-010-0079-x

7AuthorsLin S.-Y. Liu C.-L. Chang Y.-M. Zhao J. Perlman S. Hou M.-H.
TitleStructural basis for the identification of the N-terminal domain of coronavirus nucleocapsid protein as an antiviral target.
SourceJ. Med. Chem. 57:2247-2257(2014).
PubMed ID24564608
DOI10.1021/jm500089r

8AuthorsChang C.-K. Hou M.-H. Chang C.-F. Hsiao C.-D. Huang T.-H.
TitleThe SARS coronavirus nucleocapsid protein--forms and functions.
SourceAntiviral. Res. 103:39-50(2014).
PubMed ID24418573
DOI10.1016/j.antiviral.2013.12.009

9AuthorsSzelazek B. Kabala W. Kus K. Zdzalik M. Twarda-Clapa A. Golik P. Burmistrz M. Florek D. Wladyka B. Pyrc K. Dubin G.
TitleStructural Characterization of Human Coronavirus NL63 N Protein.
SourceJ. Virol. 91:0-0(2017).
PubMed ID28331093
DOI10.1128/JVI.02503-16

E1Titlehttps://viralzone.expasy.org/30?outline=all_by_species



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