|PROSITE documentation PDOC51928 [for PROSITE entry PS51929]|
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 α1–4β1β2α5 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.
PROSITE methods (with tools and information) covered by this documentation:
|1||Authors||Chang 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.|
|Title||Modular organization of SARS coronavirus nucleocapsid protein.|
|Source||J. Biomed. Sci. 13:59-72(2006).|
|2||Authors||Chang C.-K. Hsu Y.-L. Chang Y.-H. Chao F.-A. Wu M.-C. Huang Y.-S. Hu C.-K. Huang T.-H.|
|Title||Multiple nucleic acid binding sites and intrinsic disorder of severe acute respiratory syndrome coronavirus nucleocapsid protein: implications for ribonucleocapsid protein packaging.|
|Source||J. Virol. 83:2255-2264(2009).|
|3||Authors||Zuwala 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.|
|Title||The nucleocapsid protein of human coronavirus NL63.|
|Source||PLoS One. 10:E0117833-E0117833(2015).|
|4||Authors||Saikatendu K.S. Joseph J.S. Subramanian V. Neuman B.W. Buchmeier M.J. Stevens R.C. Kuhn P.|
|Title||Ribonucleocapsid formation of severe acute respiratory syndrome coronavirus through molecular action of the N-terminal domain of N protein.|
|Source||J. Virol. 81:3913-3921(2007).|
|5||Authors||Fan H. Ooi A. Tan Y.W. Wang S. Fang S. Liu D.X. Lescar J.|
|Title||The nucleocapsid protein of coronavirus infectious bronchitis virus: crystal structure of its N-terminal domain and multimerization properties.|
|6||Authors||Ma Y. Tong X. Xu X. Li X. Lou Z. Rao Z.|
|Title||Structures of the N- and C-terminal domains of MHV-A59 nucleocapsid protein corroborate a conserved RNA-protein binding mechanism in coronavirus.|
|Source||Protein. Cell. 1:688-697(2010).|
|7||Authors||Lin S.-Y. Liu C.-L. Chang Y.-M. Zhao J. Perlman S. Hou M.-H.|
|Title||Structural basis for the identification of the N-terminal domain of coronavirus nucleocapsid protein as an antiviral target.|
|Source||J. Med. Chem. 57:2247-2257(2014).|
|8||Authors||Chang C.-K. Hou M.-H. Chang C.-F. Hsiao C.-D. Huang T.-H.|
|Title||The SARS coronavirus nucleocapsid protein--forms and functions.|
|Source||Antiviral. Res. 103:39-50(2014).|
|9||Authors||Szelazek B. Kabala W. Kus K. Zdzalik M. Twarda-Clapa A. Golik P. Burmistrz M. Florek D. Wladyka B. Pyrc K. Dubin G.|
|Title||Structural Characterization of Human Coronavirus NL63 N Protein.|
|Source||J. Virol. 91:0-0(2017).|