Database accession: MF7000596
Name: S100A4 with Ca
PDB ID: 3cga
Experimental method: X-ray (2.03 Å)
Assembly: Homodimer
Source organism: Homo sapiens
Primary publication of the structure:
Pathuri P, Vogeley L, Luecke H
Crystal structure of metastasis-associated protein S100A4 in the active calcium-bound form.
(2008) J. Mol. Biol. 383: 62-77
PMID: 18783790
Abstract:
S100A4 (metastasin) is a member of the S100 family of calcium-binding proteins that is directly involved in tumorigenesis. Until recently, the only structural information available was the solution NMR structure of the inactive calcium-free form of the protein. Here we report the crystal structure of human S100A4 in the active calcium-bound state at 2.03 A resolution that was solved by molecular replacement in the space group P6(5) with two molecules in the asymmetric unit from perfectly merohedrally twinned crystals. The Ca(2+)-bound S100A4 structure reveals a large conformational change in the three-dimensional structure of the dimeric S100A4 protein upon calcium binding. This calcium-dependent conformational change opens up a hydrophobic binding pocket that is capable of binding to target proteins such as annexin A2, the tumor-suppressor protein p53 and myosin IIA. The structure of the active form of S100A4 provides insight into its interactions with its binding partners and a better understanding of its role in metastasis.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
actin binding actin binding
calcium ion binding calcium ion binding
calcium-dependent protein binding calcium-dependent protein binding
chemoattractant activity chemoattractant activity
identical protein binding identical protein binding
RAGE receptor binding RAGE receptor binding
RNA binding RNA binding
transition metal ion binding transition metal ion binding
Biological process:
epithelial to mesenchymal transition epithelial to mesenchymal transition
positive regulation of canonical NF-kappaB signal transduction positive regulation of canonical NF-kappaB signal transduction
Cellular component:
collagen-containing extracellular matrix collagen-containing extracellular matrix
cytosol cytosol
extracellular exosome extracellular exosome
extracellular region extracellular region
extracellular space extracellular space
nucleoplasm nucleoplasm
nucleus nucleus
perinuclear region of cytoplasm perinuclear region of cytoplasm
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Protein S100-A4
Source organism: Homo sapiens
Length: 101 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMACPLEKALDVMVSTFHKYSGKEGDKFKLNKSELKELLTRELPSFLGKRTDEAAFQKLMSNLDSNRDNEVDFQEYCVFLSCIAMMCNEFFEGFPDKQPRKK
UniProtKB AC: P26447 (positions: 4-90)
Coverage: 86%
Name: Protein S100-A4
Source organism: Homo sapiens
Length: 101 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMACPLEKALDVMVSTFHKYSGKEGDKFKLNKSELKELLTRELPSFLGKRTDEAAFQKLMSNLDSNRDNEVDFQEYCVFLSCIAMMCNEFFEGFPDKQPRKK
UniProtKB AC: P26447 (positions: 4-90)
Coverage: 86%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: S-100/ICaBP type EF hand dimer
Evidence level: Direct evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
GuHCl-induced denaturation of the S100B protein dimer showed that it follows a two-state unfolding/refolding process (PMID:11888280). Other S100 proteins also showed two-state unfolding, no folded monomers were observed (PMID:18346834, PMID:18706914). The dimer has a globular and compact structure with the four helices in each subunit aligning to form a unicornate-type four-helix bundle (PMID:11790100). The hydrophobic core extends through the dimer interface.
Chain A:
N/A
Chain B:
N/A
Surface and contacts features:
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). Download the CIF file (.cif)
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