Nsp12
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Nsp12
Nsp12 is a non-structural protein in the Coronavirus genome. Its gene is part of the ORF1ab reading frame and it is part of the pp1ab polyprotein; it is cleaved by 3CLpro, 3CLpro. Nsp12 is a multi-domain subunit: it consists of an N-terminal nidovirus-specific extension (NiRAN) domain, an interface domain, and a C-terminal RNA-dependent RNA polymerase, RNA-dependent RNA-polymerase domain. The N-terminal portion of SARS-CoV-2 nsp12 additionally contains a β-hairpin which is sandwiched between the NiRAN and RdRp domain. Coronavirus nsp12 also plays a role in host immune evasion; research has demonstrated that nsp12 inhibits the nuclear translocation of IRF3. RdRp Domain The RNA-dependent RNA polymerase domain of nsp12 is C-terminal. In SARS-CoV-2 the domain spans residues 366 to 920. The structure of the RdRp domain shares common structural features with eukaryotic RNA polymerase, RNA polymerases: the structure consists of a cupped right hand with subdomains referred to as finge ...
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ORF1ab
ORF1ab (also ORF1a/b) refers collectively to two open reading frames (ORFs), ORF1a and ORF1b, that are conserved in the genomes of nidoviruses, a group of viruses that includes coronaviruses. The genes express large polyproteins that undergo proteolysis to form several nonstructural proteins with various functions in the viral life cycle, including proteases and the components of the replicase-transcriptase complex (RTC). Together the two ORFs are sometimes referred to as the replicase gene. They are related by a programmed ribosomal frameshift that allows the ribosome to continue translating past the stop codon at the end of ORF1a, in a -1 reading frame. The resulting polyproteins are known as pp1a and pp1ab. Expression ORF1a is the first open reading frame at the 5' end of the genome. Together ORF1ab occupies about two thirds of the genome, with the remaining third at the 3' end encoding the structural proteins and accessory proteins. It is translated from a 5' capped ...
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Coronavirus
Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds. In humans and birds, they cause respiratory tract infections that can range from mild to lethal. Mild illnesses in humans include some cases of the common cold (which is also caused by other viruses, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS and COVID-19. In cows and pigs they cause diarrhea, while in mice they cause hepatitis and encephalomyelitis. Coronaviruses constitute the subfamily ''Orthocoronavirinae'', in the family ''Coronaviridae'', order ''Nidovirales'' and realm ''Riboviria''. They are enveloped viruses with a Positive-strand RNA virus, positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses ranges from approximately 26 to 32 kilobases, one of the largest among RNA viruses. They have characteristic club-shaped Spike protein, spikes that project from their surface, which in electron ...
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Coronavirus Proteins
Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds. In humans and birds, they cause respiratory tract infections that can range from mild to lethal. Mild illnesses in humans include some cases of the common cold (which is also caused by other viruses, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS and COVID-19. In cows and pigs they cause diarrhea, while in mice they cause hepatitis and encephalomyelitis. Coronaviruses constitute the subfamily ''Orthocoronavirinae'', in the family ''Coronaviridae'', order ''Nidovirales'' and realm ''Riboviria''. They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses ranges from approximately 26 to 32 kilobases, one of the largest among RNA viruses. They have characteristic club-shaped spikes that project from their surface, which in electron micrographs create an image reminisce ...
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N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amine group is bonded to the carboxylic group of another amino acid, making it a chain. That leaves a free carboxylic group at one end of the peptide, called the C-terminus, and a free amine group on the other end called the N-terminus. By convention, peptide sequences are written N-terminus to C-terminus, left to right (in LTR writing systems). This correlates the translation direction to the text direction, because when a protein is translated from messenger RNA, it is created from the N-terminus to the C-terminus, as amino acids are added to the carboxyl end of the protein. Chemistry Each amino acid has an amine group and a carboxylic group. Amino acids link to one another by peptide bonds which form through a dehydration reaction that j ...
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Nidovirus
''Nidovirales'' is an order of enveloped, positive-strand RNA viruses which infect vertebrates and invertebrates. Host organisms include mammals, birds, reptiles, amphibians, fish, arthropods, molluscs, and helminths. The order includes the families ''Coronaviridae'', ''Arteriviridae, Roniviridae,'' '' Tobaniviridae'', and ''Mesoniviridae''. Member viruses have a viral envelope and a positive-sense, single-stranded RNA genome which is capped and polyadenylated. Nidoviruses are named for the Latin ''nidus'', meaning nest, as all viruses in this order produce a 3' co-terminal nested set of subgenomic mRNAs during infection. Virology Structure Nidoviruses have a viral envelope and a positive-sense, single-stranded RNA genome which is capped and polyadenylated. The group expresses structural proteins separately from the nonstructural ones. The structural proteins are encoded at the 3' region of the genome and are expressed from a set of subgenomic mRNAs. Member viruses enco ...
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C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is translated from messenger RNA, it is created from N-terminus to C-terminus. The convention for writing peptide sequences is to put the C-terminal end on the right and write the sequence from N- to C-terminus. Chemistry Each amino acid has a carboxyl group and an amine group. Amino acids link to one another to form a chain by a dehydration reaction which joins the amine group of one amino acid to the carboxyl group of the next. Thus polypeptide chains have an end with an unbound carboxyl group, the C-terminus, and an end with an unbound amine group, the N-terminus. Proteins are naturally synthesized starting from the N-terminus and ending at the C-terminus. Function C-terminal retention signals While the N-terminus of a prote ...
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RNA-dependent RNA Polymerase
RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the self-replication, replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand Complementarity (molecular biology), complementary to a given RNA template. This is in contrast to typical DNA-dependent RNA polymerases, which all organisms use to catalyze the transcription (genetics), transcription of RNA from a DNA template. RdRp is an essential protein encoded in the genomes of most RNA-containing viruses that lack a DNA stage, including SARS-CoV-2. Some eukaryotes also contain RdRps, which are involved in RNA interference and differ structurally from viral RdRps. History Viral RdRps were discovered in the early 1960s from studies on mengovirus and polio virus when it was observed that these viruses were not sensitive to actinomycin D, a drug that inhibits cellular DNA-directed RNA synthesis. This lack of sensitivity suggested the action of a virus-specific ...
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β-hairpin
The beta hairpin (sometimes also called beta-ribbon or beta-beta unit) is a simple protein structural motif involving two beta strands that look like a hairpin. The motif consists of two strands that are adjacent in primary structure, oriented in an antiparallel direction (the N-terminus of one sheet is adjacent to the C-terminus of the next), and linked by a short loop of two to five amino acids. Beta hairpins can occur in isolation or as part of a series of hydrogen bonded strands that collectively comprise a beta sheet. Researchers such as Francisco Blanco ''et al.'' have used protein NMR to show that beta-hairpins can be formed from isolated short peptides in aqueous solution, suggesting that hairpins could form nucleation sites for protein folding. Classification Beta hairpins were originally categorized solely by the number of amino acid residues in their loop sequences, such that they were named one-residue, two-residue, etc. This system, however, is somewhat ambiguous ...
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SARS Genome And Nsp12
Severe acute respiratory syndrome (SARS) is a viral respiratory disease of zoonotic origin caused by the virus SARS-CoV-1, the first identified strain of the SARS-related coronavirus. The first known cases occurred in November 2002, and the syndrome caused the 2002–2004 SARS outbreak. In 2004, Xue Wu Zhang and Yee Leng Yap found that the Spike 2 (S2) protein of SARS is structurally similar to HIV-1 gp41 subunit, suggesting an analogous membrane fusion mechanism between the two. In the 2010s, Chinese scientists traced the virus through the intermediary of Asian palm civets to cave-dwelling horseshoe bats in Xiyang Yi Ethnic Township, Yunnan.The locality was referred to be "a cave in Kunming" in earlier sources because the Xiyang Yi Ethnic Township is administratively part of Kunming, though 70 km apart. Xiyang was identified on * For an earlier interview of the researchers about the locality of the caves, see: SARS was a relatively rare disease; at the end of the epidemic in J ...
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3CLpro
The 3C-like protease (3CLpro) or main protease (Mpro), formally known as C30 endopeptidase or 3-chymotrypsin-like protease, is the main protease found in coronaviruses. It cleaves the coronavirus polyprotein at eleven conserved sites. It is a cysteine protease and a member of the PA clan of proteases. It has a cysteine-histidine catalytic dyad at its active site and cleaves a Gln–( Ser/ Ala/ Gly) peptide bond. The Enzyme Commission refers to this family as SARS coronavirus main proteinase (Mpro; ). The 3CL protease corresponds to coronavirus nonstructural protein 5 (nsp5). The "3C" in the common name refers to the 3C protease (3Cpro) which is a homologous protease found in picornaviruses. Function The 3C-like protease is able to catalytically cleave a peptide bond between a glutamine at position P1 and a small amino acid (serine, alanine, or glycine) at position P1'. The SARS coronavirus 3CLpro can for instance self-cleave the following peptides: The protease is im ...
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SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19, the respiratory illness responsible for the COVID-19 pandemic. The virus previously had the Novel coronavirus, provisional name 2019 novel coronavirus (2019-nCoV), and has also been called human coronavirus 2019 (HCoV-19 or hCoV-19). First identified in the city of Wuhan, Hubei, China, the World Health Organization designated the outbreak a public health emergency of international concern from January 30, 2020, to May 5, 2023. SARS‑CoV‑2 is a positive-sense single-stranded RNA virus that is Contagious disease, contagious in humans. SARS‑CoV‑2 is a strain of the species ''Betacoronavirus pandemicum'' (SARSr-CoV), as is SARS-CoV-1, the virus that caused the 2002–2004 SARS outbreak. There are animal-borne coronavirus strains more closely related to SARS-CoV-2, the most closely known relative being the BANAL-52 bat coronavirus. SARS-CoV-2 is of Zoonosis, z ...
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RNA Polymerase
In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that catalyzes the chemical reactions that synthesize RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the double-stranded DNA so that one strand of the exposed nucleotides can be used as a template for the synthesis of RNA, a process called transcription. A transcription factor and its associated transcription mediator complex must be attached to a DNA binding site called a promoter region before RNAP can initiate the DNA unwinding at that position. RNAP not only initiates RNA transcription, it also guides the nucleotides into position, facilitates attachment and elongation, has intrinsic proofreading and replacement capabilities, and termination recognition capability. In eukaryotes, RNAP can build chains as long as 2.4 million nucleotides. RNAP produces RNA that, functionally, is either for protei ...
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