Replication protein E1

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==Function==
==Function==
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'''Replication protein E1''' (RPE1) is a human papillomavirus (HPV) essential protein which is required for its replication. RPE1 recognizes the HPV origin of replication (ori) with the aid of '''regulatory protein E2''' (RPE2). The resultant helicase complex initiates DNA unwinding to provide the template of progeny DNA synthesis, The HPV ori contains one RPE1 binding site and 2 RPE2 binding sites<ref>PMID:12086149</ref>. RPE2 is found also in bovine papillomavirus (BPV).
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'''Replication protein E1''' (RPE1) is a human papillomavirus (HPV) essential protein which is required for its replication. RPE1 recognizes the HPV origin of replication (ori) with the aid of '''regulatory protein E2''' (RPE2). The resultant helicase complex initiates DNA unwinding to provide the template of progeny DNA synthesis, The HPV ori contains one RPE1 binding site and 2 RPE2 binding sites<ref>PMID:12086149</ref>. RPE1 is found also in bovine papillomavirus (BPV).
== Disease ==
== Disease ==
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RPE2 induces apoptosis of its host cells<ref>PMID:26906543</ref>.
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RPE1 has been shown to mitigate host cell defenses leading to the development of cancer induces apoptosis of its host cells<ref>PMID:29495005</ref>.
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==Relevance==
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The detection of RPE1 mRNA and promoter methylation may serve as cancer prognostic marker.
== Structural highlights ==
== Structural highlights ==
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The complex between HPV6a DBD and 18-bp DNA (PDB code [[2ayg]]) shows the binding of 2 recognition helices of the dimer to 2 successive major grooves of the target DNA making numerous contacts to the DNA backbone phosphate atoms and to its bases<ref>PMID:16914454</ref>.
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The complex between BPV1 DBD and 21-bp DNA (PDB code [[1ksx]]) shows 2 DBD-DNA binding modules: a binding loop and a binding helix each interacting with a single strand. The protein-DNA interactions are hydrophilic to phosphate atoms and van der Waals hydrophobic ones<ref>PMID:11889054</ref>.
</StructureSection>
</StructureSection>
==3D structures of replication protein E1==
==3D structures of replication protein E1==

Revision as of 11:13, 27 January 2021

Bovine papillomavirus 1 replication protein E1 complex with DNA (PDB code 1ksx)

Drag the structure with the mouse to rotate

3D structures of replication protein E1

Updated on 27-January-2021

Domains: helicase 301-605; DNA-binding (DBD) 286-365

1r9w - RPE1 DBD - HPV18
1tue - RPE1 428-631 (mutant) + RPE2 TAD
2v9p - RPE1 helicase domain - BPV1
5a9k - RPE1 helicase domain - Cryo EM
2gxa - RPE1 helicase domain + DNA + ADP
1f08 - RPE1 DBD
1ksx, 1ksy - RPE1 DBD + DNA

References

  1. Wilson VG, West M, Woytek K, Rangasamy D. Papillomavirus E1 proteins: form, function, and features. Virus Genes. 2002 Jun;24(3):275-90. doi: 10.1023/a:1015336817836. PMID:12086149 doi:http://dx.doi.org/10.1023/a:1015336817836
  2. Baedyananda F, Chaiwongkot A, Bhattarakosol P. Elevated HPV16 E1 Expression Is Associated with Cervical Cancer Progression. Intervirology. 2017;60(5):171-180. doi: 10.1159/000487048. Epub 2018 Mar 1. PMID:29495005 doi:http://dx.doi.org/10.1159/000487048
  3. Enemark EJ, Stenlund A, Joshua-Tor L. Crystal structures of two intermediates in the assembly of the papillomavirus replication initiation complex. EMBO J. 2002 Mar 15;21(6):1487-96. PMID:11889054 doi:http://dx.doi.org/10.1093/emboj/21.6.1487

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Michal Harel, Alexander Berchansky

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