General Information

Database Accession: DI3000006

Name: TNF receptor associated factor 2 in complex with a peptide from TNF-R2

PDB ID: 1ca9 PDB

Experimental method: X-ray (2.30 Å)

Source organism: Homo sapiens

Proof of disorder: Inferred from motif

Primary publication of the structure:

Park YC, Burkitt V, Villa AR, Tong L, Wu H
Structural basis for self-association and receptor recognition of human TRAF2.
(1999) Nature 398: 533-8

PMID: 10206649 PubMed

Abstract:

Tumour necrosis factor (TNF)-receptor-associated factors (TRAFs) form a family of cytoplasmic adapter proteins that mediate signal transduction from many members of the TNF-receptor superfamily and the interleukin-1 receptor. They are important in the regulation of cell survival and cell death. The carboxy-terminal region of TRAFs (the TRAF domain) is required for self-association and interaction with receptors. The domain contains a predicted coiled-coil region that is followed by a highly conserved TRAF-C domain. Here we report the crystal structure of the TRAF domain of human TRAF2, both alone and in complex with a peptide from TNF receptor-2 (TNF-R2). The structures reveal a trimeric self-association of the TRAF domain, which we confirm by studies in solution. The TRAF-C domain forms a new, eight-stranded antiparallel beta-sandwich structure. The TNF-R2 peptide binds to a conserved shallow surface depression on one TRAF-C domain and does not contact the other protomers of the trimer. The nature of the interaction indicates that an SXXE motif may be a TRAF2-binding consensus sequence. The trimeric structure of the TRAF domain provides an avidity-based explanation for the dependence of TRAF recruitment on the oligomerization of the receptors by their trimeric extracellular ligands.

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

Molecular function:

ubiquitin protein ligase binding Interacting selectively and non-covalently with a ubiquitin protein ligase enzyme, any of the E3 proteins. GeneOntology

Biological process:

tumor necrosis factor-mediated signaling pathway A series of molecular signals initiated by the binding of a tumor necrosis factor to a receptor on the surface of a cell, and ending with regulation of a downstream cellular process, e.g. transcription. GeneOntology

regulation of cysteine-type endopeptidase activity involved in apoptotic process Any process that modulates the activity of a cysteine-type endopeptidase involved in apoptosis. GeneOntology

positive regulation of proteolysis Any process that activates or increases the frequency, rate or extent of the hydrolysis of a peptide bond or bonds within a protein. GeneOntology

intracellular signal transduction The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell. GeneOntology

negative regulation of apoptotic process Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process. GeneOntology

cellular response to stress Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating the organism is under stress. The stress is usually, but not necessarily, exogenous (e.g. temperature, humidity, ionizing radiation). GeneOntology

regulation of gene expression Any process that modulates 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

extrinsic apoptotic signaling pathway A series of molecular signals in which a signal is conveyed from the cell surface to trigger the apoptotic death of a cell. The pathway starts with either a ligand binding to a cell surface receptor, or a ligand being withdrawn from a cell surface receptor (e.g. in the case of signaling by dependence receptors), and ends when the execution phase of apoptosis is triggered. GeneOntology

cellular response to oxygen-containing compound Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an oxygen-containing compound stimulus. GeneOntology

Cellular component:

membrane raft Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions. GeneOntology

nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. GeneOntology

cytoplasm All of the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. GeneOntology

vesicle membrane The lipid bilayer surrounding any membrane-bounded vesicle in the cell. GeneOntology

integral component of plasma membrane The component of the plasma membrane consisting of the gene products and protein complexes having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane. GeneOntology

Structure Summary Structural annotations of the participating protein chains.

Entry contents: 4 distinct polypeptide molecules

Chains: G, A, B, C

Notes: Chains D, E, F and H were removed as chains A, B, C and G highlight the biologically relevant interaction.

Chain G

Name: Tumor necrosis factor receptor superfamily member 1B Disordered Inferred from motif

Source organism: Homo sapiens

Length: 9 residues

Sequence:Sequence according to PDB SEQRESQVPFSKEEC

UniProtKB AC: P20333 (positions: 420-428) UniProt Coverage: 2%

UniRef90 AC: UniRef90_P20333 (positions: 420-428) UniRef90

Chain A

Name: TNF receptor-associated factor 2 Ordered component

Source organism: Homo sapiens

Length: 192 residues

Sequence:Sequence according to PDB SEQRESDQDKIEALSSKVQQLERSIGLKDLAMADLEQKVLEMEASTYDGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVVMKGPNDALLRWPFNQKVTLMLLDQNNREHVIDAFRPDVTSSSFQRPVNDMNIASGCPLFCPVSKMEAKNSYVRDDAIFIKAIVDLTGL

UniProtKB AC: Q12933 (positions: 310-501) UniProt Coverage: 38.3%

UniRef90 AC: UniRef90_Q12933 (positions: 310-501) UniRef90

Chain B

Name: TNF receptor-associated factor 2 Ordered component

Source organism: Homo sapiens

Length: 192 residues

Sequence:Sequence according to PDB SEQRESDQDKIEALSSKVQQLERSIGLKDLAMADLEQKVLEMEASTYDGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVVMKGPNDALLRWPFNQKVTLMLLDQNNREHVIDAFRPDVTSSSFQRPVNDMNIASGCPLFCPVSKMEAKNSYVRDDAIFIKAIVDLTGL

UniProtKB AC: Q12933 (positions: 310-501) UniProt Coverage: 38.3%

UniRef90 AC: UniRef90_Q12933 (positions: 310-501) UniRef90

Chain C

Name: TNF receptor-associated factor 2 Ordered component

Source organism: Homo sapiens

Length: 192 residues

Sequence:Sequence according to PDB SEQRESDQDKIEALSSKVQQLERSIGLKDLAMADLEQKVLEMEASTYDGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVVMKGPNDALLRWPFNQKVTLMLLDQNNREHVIDAFRPDVTSSSFQRPVNDMNIASGCPLFCPVSKMEAKNSYVRDDAIFIKAIVDLTGL

UniProtKB AC: Q12933 (positions: 310-501) UniProt Coverage: 38.3%

UniRef90 AC: UniRef90_Q12933 (positions: 310-501) UniRef90

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

Chain G: Disordered Inferred from motif

The protein region involved in the interaction contains a known functional linear motif (LIG_TRAF2_1).

Chain A: Ordered component

The MATH domain involved in the interaction is known to adopt a stable structure in isolation in trimeric form. A solved structure of the domain trimer without bound ligands is represented by PDB ID 1ca4.

Chain B: Ordered component

The MATH domain involved in the interaction is known to adopt a stable structure in isolation in trimeric form. A solved structure of the domain trimer without bound ligands is represented by PDB ID 1ca4.

Chain C: Ordered component

The MATH domain involved in the interaction is known to adopt a stable structure in isolation in trimeric form. A solved structure of the domain trimer without bound ligands is represented by PDB ID 1ca4.

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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