SARS-CoV-2 protein NSP8
From Proteopedia
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| - | + | <SX viewer='molstar' load='6yyt' size='340' side='right' caption=' Structure of replicating SARS-CoV-2 polymerase (PDB code [[6yyt]]).' scene=''> | |
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==Function== | ==Function== | ||
| - | Two different conformations of nsp8 and one [[SARS-CoV-2_protein_NSP7|nsp7]] work as a co-factor for [[SARS-CoV-2 enzyme RdRp|nsp12]] . Together, | + | Two different conformations of '''nsp8''' and one [[SARS-CoV-2_protein_NSP7|nsp7]] work as a co-factor for [[SARS-CoV-2 enzyme RdRp|nsp12]]. Together, these four proteins form the minimal core polymerase complex. Without its co-factors nsp12 has a low efficiency in polymerase activity. This complex plays a key role in RNA synthesis of the virus, making it an important player in the replication procedure<ref name="Peng"> PMID: 32531208</ref>. It has been suggested that the nsp7-nsp8 dimer might act as a primase in the complex<ref name="Konkolova"> PMID: 32535228</ref>. |
==Disease== | ==Disease== | ||
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The nsp8 is encoded on the open reading frame ORF1a, contains 198 amino acids<ref name="Konkolova"/> and has two subdomains. The first domain has an α-turn-α motif (α1: E77-L98 and α2: D101-D112). The second domain has four antiparallel β-strands consisting the C-terminal subdomain (β1: A125-I132, β2: T146-Y149, β3: A152- V160, β4: L184-R190) with an inserted α3 (Y135-T141) <ref name="Konkolova"/>. | The nsp8 is encoded on the open reading frame ORF1a, contains 198 amino acids<ref name="Konkolova"/> and has two subdomains. The first domain has an α-turn-α motif (α1: E77-L98 and α2: D101-D112). The second domain has four antiparallel β-strands consisting the C-terminal subdomain (β1: A125-I132, β2: T146-Y149, β3: A152- V160, β4: L184-R190) with an inserted α3 (Y135-T141) <ref name="Konkolova"/>. | ||
Depending on whether the nsp8 (nsp8.1) forms a dimer with nsp7 to bind to nsp12 or binds as a monomer (nsp8.2) to nsp12, it forms significantly different conformations. The N-terminal extension helix shows substantial refolding<ref name="Peng"/>. | Depending on whether the nsp8 (nsp8.1) forms a dimer with nsp7 to bind to nsp12 or binds as a monomer (nsp8.2) to nsp12, it forms significantly different conformations. The N-terminal extension helix shows substantial refolding<ref name="Peng"/>. | ||
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The nsp7-nsp8.1 heterodimer binds to nsp12 above the thumb domain of the RNA-dependent RNA polymerase (RdRp), mostly mediated by nsp7. With this interaction, the conformation of the finger extension loops of the nsp12 are stabilized<ref name="Peng"/>. The dimerization interface of the nsp7-nsp8 heterodimer has an area of 1340 Ų and is formed by the α1 and α2 of nsp8 and the α1 and α3 helices of nsp7<ref name="Konkolova"/>. | The nsp7-nsp8.1 heterodimer binds to nsp12 above the thumb domain of the RNA-dependent RNA polymerase (RdRp), mostly mediated by nsp7. With this interaction, the conformation of the finger extension loops of the nsp12 are stabilized<ref name="Peng"/>. The dimerization interface of the nsp7-nsp8 heterodimer has an area of 1340 Ų and is formed by the α1 and α2 of nsp8 and the α1 and α3 helices of nsp7<ref name="Konkolova"/>. | ||
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The nsp8.2 monomer forms interactions with the top region of the finger subdomain and the interface domain of nsp12. | The nsp8.2 monomer forms interactions with the top region of the finger subdomain and the interface domain of nsp12. | ||
A prominent feature of both nsp8 subunits are the long α-helical extensions up to 28 base pairs away from the active site. The residues of the RdRp flanking the exiting RNA are positively charged. These only become ordered when interacting with the exiting RNA duplex<ref name="Hillen"> PMID: 32438371 </ref>. | A prominent feature of both nsp8 subunits are the long α-helical extensions up to 28 base pairs away from the active site. The residues of the RdRp flanking the exiting RNA are positively charged. These only become ordered when interacting with the exiting RNA duplex<ref name="Hillen"> PMID: 32438371 </ref>. | ||
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== See also == | == See also == | ||
| - | [[Coronavirus_Disease 2019 (COVID-19)]] | + | [[Coronavirus_Disease 2019 (COVID-19)]]<br> |
| + | [[SARS-CoV-2_virus_proteins]]<br> | ||
| + | [[COVID-19 AlphaFold2 Models]] | ||
__NOTOC__ | __NOTOC__ | ||
</SX> | </SX> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
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References
- ↑ 1.0 1.1 1.2 1.3 1.4 Peng Q, Peng R, Yuan B, Zhao J, Wang M, Wang X, Wang Q, Sun Y, Fan Z, Qi J, Gao GF, Shi Y. Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2. Cell Rep. 2020 Jun 16;31(11):107774. doi: 10.1016/j.celrep.2020.107774. Epub 2020, May 30. PMID:32531208 doi:http://dx.doi.org/10.1016/j.celrep.2020.107774
- ↑ 2.0 2.1 2.2 2.3 Konkolova E, Klima M, Nencka R, Boura E. Structural analysis of the putative SARS-CoV-2 primase complex. J Struct Biol. 2020 Aug 1;211(2):107548. doi: 10.1016/j.jsb.2020.107548. Epub, 2020 Jun 11. PMID:32535228 doi:http://dx.doi.org/10.1016/j.jsb.2020.107548
- ↑ Hillen HS, Kokic G, Farnung L, Dienemann C, Tegunov D, Cramer P. Structure of replicating SARS-CoV-2 polymerase. Nature. 2020 May 21. pii: 10.1038/s41586-020-2368-8. doi:, 10.1038/s41586-020-2368-8. PMID:32438371 doi:http://dx.doi.org/10.1038/s41586-020-2368-8
- ↑ Yoshimoto FK. The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19. Protein J. 2020 Jun;39(3):198-216. doi: 10.1007/s10930-020-09901-4. PMID:32447571 doi:http://dx.doi.org/10.1007/s10930-020-09901-4
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