General Information

Database Accession: DI1020013

Name: Retinoblastoma protein pocket domain in complex with adenovirus E1A CR1 domain

PDB ID: 2r7g PDB

Experimental method: X-ray (1.67 Å)

Source organism: Human adenovirus C serotype 5 / Homo sapiens

Proof of disorder: Confirmed

K_d: 9.00×10^-07 M PubMed

Primary publication of the structure:

Liu X, Marmorstein R
Structure of the retinoblastoma protein bound to adenovirus E1A reveals the molecular basis for viral oncoprotein inactivation of a tumor suppressor.
(2007) Genes Dev. 21: 2711-6

PMID: 17974914 PubMed

Abstract:

The adenovirus (Ad) E1A (Ad-E1A) oncoprotein mediates cell transformation, in part, by displacing E2F transcription factors from the retinoblastoma protein (pRb) tumor suppressor. In this study we determined the crystal structure of the pRb pocket domain in complex with conserved region 1 (CR1) of Ad5-E1A. The structure and accompanying biochemical studies reveal that E1A-CR1 binds at the interface of the A and B cyclin folds of the pRb pocket domain, and that both E1A-CR1 and the E2F transactivation domain use similar conserved nonpolar residues to engage overlapping sites on pRb, implicating a novel molecular mechanism for pRb inactivation by a viral oncoprotein.

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

Molecular function:

activating transcription factor binding Interacting selectively and non-covalently with an activating transcription factor, any protein whose activity is required to initiate or upregulate transcription. GeneOntology

Biological process:

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

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

viral process A multi-organism process in which a virus is a participant. The other participant is the host. Includes infection of a host cell, replication of the viral genome, and assembly of progeny virus particles. In some cases the viral genetic material may integrate into the host genome and only subsequently, under particular circumstances, 'complete' its life cycle. GeneOntology

regulation of cell cycle Any process that modulates the rate or extent of progression through the cell cycle. GeneOntology

negative regulation of gene expression Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product or products (proteins or RNA). This includes the production of an RNA transcript as well as any processing to produce a mature RNA product or an mRNA (for protein-coding genes) and the translation of that mRNA into protein. Protein maturation is included when required to form an active form of a product from an inactive precursor form. GeneOntology

regulation of protein modification process Any process that modulates the frequency, rate or extent of the covalent alteration of one or more amino acid residues within a protein. GeneOntology

regulation of cell proliferation Any process that modulates the frequency, rate or extent of cell proliferation. GeneOntology

negative regulation of molecular function Any process that stops or reduces the rate or extent of a molecular function, an elemental biological activity occurring at the molecular level, such as catalysis or binding. GeneOntology

positive regulation of cellular process Any process that activates or increases the frequency, rate or extent of a cellular process, any of those that are carried out at the cellular level, but are not necessarily restricted to a single cell. For example, cell communication occurs among more than one cell, but occurs at the cellular level. GeneOntology

negative regulation of signal transduction Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction. GeneOntology

Cellular component: not assigned

Structure Summary Structural annotations of the participating protein chains.

Entry contents: 2 distinct polypeptide molecules

Chains: B, A

Notes: Chains C, D and E were removed as chains A and B represent the biologically relevant interaction.

Chain B

Name: Early E1A 32 kDa protein Disordered Confirmed

Source organism: Human adenovirus C serotype 5

Length: 10 residues

Sequence:Sequence according to PDB SEQRESPPTLHELYDL

UniProtKB AC: P03255 (positions: 40-49) UniProt Coverage: 3.5%

UniRef90 AC: UniRef90_P03255 (positions: 40-49) UniRef90

Chain A

Name: Retinoblastoma-associated protein Ordered

Source organism: Homo sapiens

Length: 408 residues

Sequence:Sequence according to PDB SEQRESNTIQQLMMILNSASDQPSENLISYFNNCTVNPKESILKRVKDIGYIFKEKFAKAVGQGCVEIGSQRYKLGVRLYYRVMESMLKSEEERLSIQNFSKLLNDNIFHMSLLACALEVVMATYSRSTSQNLDSGTDLSFPWILNVLNLKAFDFYKVIESFIKAEGNLTREMIKHLERCEHRIMESLAWLSDSPLFDLIKQSKDREGPTDHLESACPLNLPLQNNHTAADMYLSPVRSPKKKGSTTRVNSTANAETQATSAFQTQKPLKSTSLSLFYKKVYRLAYLRLNTLCERLLSEHPELEHIIWTLFQHTLQNEYELMRDRHLDQIMMCSMYGICKVKNIDLKFKIIVTAYKDLPHAVQETFKRVLIKEEEYDSIIVFYNSVFMQRLKTNILQYASTRPPTLSPIPHIPR

UniProtKB AC: P06400 (positions: 380-787) UniProt Coverage: 44%

UniRef90 AC: UniRef90_P06400 (positions: 380-787) UniRef90

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

Chain B: Disordered Confirmed

The 1-139 region described in IDEAL entry IID90003 covers 100% of the sequence present in the structure. The protein region involved in the interaction contains a known functional linear motif (LIG_Rb_pABgroove_1).

Chain A: Ordered

The Rb pocket domain (consist of Rb_A and Rb_B) involved in the interaction is known to adopt a stable structure in isolation (see Pfam domains PF01858 and PF01857). A solved monomeric structure of the domain is represented by DPB ID 3pom.

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).

No related structure was found in the Protein Data Bank.

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