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From Proteopedia
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==IAV RNA-Dependent RNA Polymerase== | ==IAV RNA-Dependent RNA Polymerase== | ||
| - | The RNA-dependent RNA polymerase (RdRp) is a critical protein complex for the replication and transcription of viral genes. This enzyme is of clinical significance in IAV because it is critical in the zoonosis of Influenza A viruses like swine flu. Because of its critical roles in viral replication and zoonosis, RdRp is the focus of much antiviral research. However, due to limited structural elucidation of the Influenza A RdRP, structural-based drug design to inhibit RdRp activity is also limited. Influenza A RdRp is also an especially difficult site for drug development because it is unique relative to other viral RdRps. Unlike many other viral RdRps, IAV RdRp must first enter the nucleus to transcribe and replicate viral genetic information as opposed to first initiating translation in the cytoplasm. | + | The RNA-dependent RNA polymerase (RdRp) is a critical protein complex for the replication and transcription of viral genes. This enzyme is of clinical significance in IAV because it is critical in the zoonosis of Influenza A viruses like swine flu. Because of its critical roles in viral replication and zoonosis, RdRp is the focus of much antiviral research. However, due to limited structural elucidation of the Influenza A RdRP, structural-based drug design to inhibit RdRp activity is also limited. Influenza A RdRp is also an especially difficult site for drug development because it is unique relative to other viral RdRps. Unlike many other viral RdRps, IAV RdRp must first enter the nucleus to transcribe and replicate viral genetic information as opposed to first initiating translation in the cytoplasm. To initiate transcription, primers must be taken from host RNAs through cap-snatching, wherein 5' caps are cleaved from host RNAs and transferred to viral RNA. |
==RdRp Structure== | ==RdRp Structure== | ||
IAV RdRp consists of three unique polypeptide subunits called polymerase basic 1 (PB1), polymerase basic 2 (PB2) and polymerase acidic (PA). | IAV RdRp consists of three unique polypeptide subunits called polymerase basic 1 (PB1), polymerase basic 2 (PB2) and polymerase acidic (PA). | ||
| - | The PB1 subunit constitutes the stereotypical right-handed model of RdRp, including the fingers, palm, and thumb of the hand. Motifs A-E are contained within the PB1 domain: motifs A, C, D, and E are all in the palm, and motifs B and F are in the fingers. The PB2 domain interacts with the PB1 thumb and C-terminus extension, conferring flexibility and stability to the overall complex. The PA domain spans the backside of PB1 and is responsible for the endonuclease activity of the RdRp. | + | The PB1 subunit constitutes the stereotypical right-handed model of RdRp, including the fingers, palm, and thumb of the hand. Motifs A-E are contained within the PB1 domain: motifs A, C, D, and E are all in the palm, and motifs B and F are in the fingers. The PB2 domain interacts with the PB1 thumb and C-terminus extension, conferring flexibility and stability to the overall complex. The PA domain spans the backside of PB1 and is responsible for the endonuclease activity of the RdRp. |
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| + | The PB2 also contains the cap-binding domain necessary for cap-snatching. PB2 recognizes host primers and captures host RNA, allowing PA's endonuclease domain to cleave primers away. | ||
| + | SCENE of this site | ||
== References == | == References == | ||
Revision as of 11:37, 7 October 2021
Swine Flu and RdRp
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