Replication protein E1

Function

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^[1]. RPE1 is found also in bovine papillomavirus (BPV).

Disease

RPE1 has been shown to mitigate host cell defenses leading to the development of cancer induces apoptosis of its host cells^[2].

Relevance

The detection of RPE1 mRNA and promoter methylation may serve as cancer prognostic marker.

Structural highlights

The complex between BPV1 DBD and 21-bp DNA (PDB code 1ksx) shows 2 DBD-DNA binding modules: a and a each interacting with a single strand. The protein-DNA interactions are hydrophilic to phosphate atoms and van der Waals hydrophobic ones^[3].

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

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3D structures of replication protein E13D structures of replication protein E1

Updated on 13-February-2022

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

1r9w - HpvRPE1 DBD – Human papilloma virus 18
1tue - HpvRPE1 428-631 (mutant) + RPE2 TAD
2gxa - DpvRPE1 helicase domain + DNA + ADP – Delta papilloma virus 4
5a9k - BpvRPE1 helicase domain – Bovine papilloma virus - Cryo EM
2v9p - BpvRPE1 helicase domain
1f08 - BpvRPE1 DBD
1ksx, 1ksy - BpvRPE1 DBD + DNA
7apd - BpvRPE1 helicase domain + DNA – Cryo EM

ReferencesReferences

↑ 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
↑ 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
↑ 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

[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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