General Information

Database accession: MF2140006

Name: DNA binding domain of the E2 protein (Human papillomavirus type 18)

PDB ID: 1f9f PDB

Experimental method: X-ray (1.90 Å)

Assembly: homodimer

Source organism: Human papillomavirus type 18

Primer publication of the structure:

Kim SS, Tam JK, Wang AF, Hegde RS
The structural basis of DNA target discrimination by papillomavirus E2 proteins.
(2000) J. Biol. Chem. 275: 31245-54

PMID: 10906136 PubMed

Abstract:

The papillomavirus E2 proteins regulate the transcription of all papillomavirus genes and are necessary for viral DNA replication. Disruption of the E2 gene is commonly associated with malignancy in cervical carcinoma, indicating that E2 has a role in regulating tumor progression. Although the E2 proteins from all characterized papillomaviruses bind specifically to the same 12-base pair DNA sequence, the cancer-associated human papillomavirus E2 proteins display a unique ability to detect DNA flexibility and intrinsic curvature. To understand the structural basis for this phenomenon, we have determined the crystal structures of the human papillomavirus-18 E2 DNA-binding domain and its complexes with high and low affinity binding sites. The E2 protein is a dimeric beta-barrel and the E2-DNA interaction is accompanied by a large deformation of the DNA as it conforms to the E2 surface. DNA conformation and E2-DNA contacts are similar in both high and low affinity complexes. The differences in affinity correlate with the flexibility of the DNA sequence. Preferences of E2 proteins from different papillomavirus strains for flexible or prevent DNA targets correlate with the distribution of positive charge on their DNA interaction surfaces, suggesting a role for electrostatic forces in the recognition of DNA deformability.


Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function:

DNA binding Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid). GeneOntology

nucleotide binding Interacting selectively and non-covalently with a nucleotide, any compound consisting of a nucleoside that is esterified with (ortho)phosphate or an oligophosphate at any hydroxyl group on the ribose or deoxyribose. GeneOntology

protein binding Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules). GeneOntology

transcription factor activity, sequence-specific DNA binding Interacting selectively and non-covalently with a specific DNA sequence in order to modulate transcription. The transcription factor may or may not also interact selectively with a protein or macromolecular complex. GeneOntology

Biological process:

regulation of transcription, DNA-templated Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription. GeneOntology

viral DNA genome replication The replication of a viral DNA genome. GeneOntology

regulation of DNA replication Any process that modulates the frequency, rate or extent of DNA replication. GeneOntology

transcription, DNA-templated The cellular synthesis of RNA on a template of DNA. GeneOntology

Cellular component:

host cytoskeleton Any of the various filamentous elements that form the internal framework of host cells, and typically remain after treatment of the cells with mild detergent to remove membrane constituents and soluble components of the host cytoplasm. The term embraces intermediate filaments, microfilaments, microtubules, the microtrabecular lattice, and other structures characterized by a polymeric filamentous nature and long-range order within the host cell. The various elements of the host cytoskeleton not only serve in the maintenance of host cellular shape but also have roles in other host cellular functions, including cellular movement, cell division, endocytosis, and movement of organelles. GeneOntology

host cell nucleus A membrane-bounded organelle as it is found in the host cell in which chromosomes are housed and replicated. The host is defined as the larger of the organisms involved in a symbiotic interaction. GeneOntology

Structure Summary Structural annotations of the participating protein chains.

Entry contents: 2 distinct polypeptide molecules

Chains: A, B

Notes: Chains C and D were removed as chains A and B represent the biologically active dimer.

Number of unique protein segments: 1


Chain A

Name: Regulatory protein E2

Source organism: Human papillomavirus type 18

Length: 83 residues

Sequence:Sequence according to PDB SEQRESGSHMTPIIHLKGDRNSLKCLRYRLRKHSDHYRDISSTWHWTGAGNEKTGILTVTYHSETQRTKFLNTVAIPDSVQILVGYMTM

UniProtKB AC: P06790 (positions: 283-365) UniProt Coverage: 22.7%

UniRef90 AC: UniRef90_P06790 (positions: 287-365) UniRef90

Chain B

Name: Regulatory protein E2

Source organism: Human papillomavirus type 18

Length: 83 residues

Sequence:Sequence according to PDB SEQRESGSHMTPIIHLKGDRNSLKCLRYRLRKHSDHYRDISSTWHWTGAGNEKTGILTVTYHSETQRTKFLNTVAIPDSVQILVGYMTM

UniProtKB AC: P06790 (positions: 283-365) UniProt Coverage: 22.7%

UniRef90 AC: UniRef90_P06790 (positions: 287-365) UniRef90

Evidence Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding.

Complex evidence:

The DNA binding domain of E2 was shown to exhibit a two-state concerted unfolding and dissociation in denaturation/renaturation experiments (PMID: 8745409, PMID: 8756330).

Related Structure(s) Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap).

There is 1 related structure in the Protein Data Bank:











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