General Information

Database Accession: DI1000147

Name: Smad MH2 domain bound to the Smad-binding domain of SARA

PDB ID: 1dev PDB

Experimental method: X-ray (2.20 Å)

Source organism: Homo sapiens

Proof of disorder: Confirmed

K_d: 2.40×10^-07 M PubMed

Primary publication of the structure:

Wu G, Chen YG, Ozdamar B, Gyuricza CA, Chong PA, Wrana JL, Massagué J, Shi Y
Structural basis of Smad2 recognition by the Smad anchor for receptor activation.
(2000) Science 287: 92-7

PMID: 10615055 PubMed

Abstract:

The Smad proteins mediate transforming growth factor-beta (TGFbeta) signaling from the transmembrane serine-threonine receptor kinases to the nucleus. The Smad anchor for receptor activation (SARA) recruits Smad2 to the TGFbeta receptors for phosphorylation. The crystal structure of a Smad2 MH2 domain in complex with the Smad-binding domain (SBD) of SARA has been determined at 2.2 angstrom resolution. SARA SBD, in an extended conformation comprising a rigid coil, an alpha helix, and a beta strand, interacts with the beta sheet and the three-helix bundle of Smad2. Recognition between the SARA rigid coil and the Smad2 beta sheet is essential for specificity, whereas interactions between the SARA beta strand and the Smad2 three-helix bundle contribute significantly to binding affinity. Comparison of the structures between Smad2 and a comediator Smad suggests a model for how receptor-regulated Smads are recognized by the type I receptors.

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

Molecular function:

metal ion binding Interacting selectively and non-covalently with any metal ion. GeneOntology

protein domain specific binding Interacting selectively and non-covalently with a specific domain of a protein. GeneOntology

Biological process:

transforming growth factor beta receptor signaling pathway A series of molecular signals initiated by the binding of an extracellular ligand to a transforming growth factor beta receptor on the surface of a target cell, and ending with regulation of a downstream cellular process, e.g. transcription. GeneOntology

SMAD protein complex assembly The aggregation, arrangement and bonding together of a set of components to form a protein complex that contains SMAD proteins. GeneOntology

proteolysis The hydrolysis of proteins into smaller polypeptides and/or amino acids by cleavage of their peptide bonds. GeneOntology

peptide transport The directed movement of peptides, compounds of two or more amino acids where the alpha carboxyl group of one is bound to the alpha amino group of another, into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. GeneOntology

Cellular component:

cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. GeneOntology

protein complex A stable macromolecular complex composed (only) of two or more polypeptide subunits along with any covalently attached molecules (such as lipid anchors or oligosaccharide) or non-protein prosthetic groups (such as nucleotides or metal ions). Prosthetic group in this context refers to a tightly bound cofactor. The component polypeptide subunits may be identical. GeneOntology

intracellular membrane-bounded organelle Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane and occurring within the cell. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes the plasma membrane. GeneOntology

Structure Summary Structural annotations of the participating protein chains.

Entry contents: 2 distinct polypeptide molecules

Chains: B, A

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

Chain B

Name: Zinc finger FYVE domain-containing protein 9 Disordered Confirmed

Source organism: Homo sapiens

Length: 41 residues

Sequence:Sequence according to PDB SEQRESSQSPNPNNPAEYCSTIPPLQQAQASGALSSPPPTVMVPVGV

UniProtKB AC: O95405 (positions: 771-811) UniProt Coverage: 2.9%

UniRef90 AC: UniRef90_O95405 (positions: 771-811) UniRef90

Chain A

Name: Mothers against decapentaplegic homolog 2 Ordered

Source organism: Homo sapiens

Length: 196 residues

Sequence:Sequence according to PDB SEQRESLDLQPVTYSEPAFWCSIAYYELNQRVGETFHASQPSLTVDGFTDPSNSERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIGGEVFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQM

UniProtKB AC: Q15796 (positions: 261-456) UniProt Coverage: 42%

UniRef90 AC: UniRef90_Q15796 (positions: 261-456) 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 interacting region of SARA (Smad Binding Domain) has been shown to be intrinsically disordered (PMID: 15231848; DisProt entry DP00141). The 765-853 region described in IDEAL entry IID00112 covers 100% of the sequence present in the structure.

Chain A: Ordered

The MH2 domain involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF03166). A solved monomeric structure of the domain from a homologous protein is represented by PDB ID 1mjs.

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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