Database accession: MF7000605
Name: Ca2+-loaded S100A2 with Ca
PDB ID: 4duq
Experimental method: X-ray (1.30 Å)
Assembly: Homodimer
Source organism: Homo sapiens
Primary publication of the structure:
Koch M, Fritz G
The structure of Ca2+-loaded S100A2 at 1.3-Å resolution.
(2012) FEBS J. 279: 1799-810
PMID: 22394450
Abstract:
S100A2 is an EF-hand calcium ion (Ca(2+))-binding protein that activates the tumour suppressor p53. In order to understand the molecular mechanisms underlying the Ca(2+) -induced activation of S100A2, the structure of Ca(2+)-bound S100A2 was determined at 1.3 Å resolution by X-ray crystallography. The structure was compared with Ca(2+) -free S100A2 and with other S100 proteins. Binding of Ca(2+) to S100A2 induces small structural changes in the N-terminal EF-hand, but a large conformational change in the C-terminal EF-hand, reorienting helix III by approximately 90°. This movement is accompanied by the exposure of a hydrophobic cavity between helix III and helix IV that represents the target protein interaction site. This molecular reorganization is associated with the breaking and new formation of intramolecular hydrophobic contacts. The target binding site exhibits unique features; in particular, the hydrophobic cavity is larger than in other Ca(2+)-loaded S100 proteins. The structural data underline that the shape and size of the hydrophobic cavity are major determinants for target specificity of S100 proteins and suggest that the binding mode for S100A2 is different from that of other p53-interacting S100 proteins. Database Structural data are available in the Protein Data Bank database under the accession number 4DUQ
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
calcium ion binding calcium ion binding
calcium-dependent protein binding calcium-dependent protein binding
identical protein binding identical protein binding
transition metal ion binding transition metal ion binding
Biological process:
endothelial cell migration endothelial cell migration
Cellular component: not assigned
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-A2
Source organism: Homo sapiens
Length: 98 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMMCSSLEQALAVLVTTFHKYSCQEGDKFKLSKGEMKELLHKELPSFVGEKVDEEGLKKLMGSLDENSDQQVDFQEYAVFLALITVMCNDFFQGCPDRP
UniProtKB AC: P29034 (positions: 3-90)
Coverage: 89%
Name: Protein S100-A2
Source organism: Homo sapiens
Length: 98 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMMCSSLEQALAVLVTTFHKYSCQEGDKFKLSKGEMKELLHKELPSFVGEKVDEEGLKKLMGSLDENSDQQVDFQEYAVFLALITVMCNDFFQGCPDRP
UniProtKB AC: P29034 (positions: 3-92)
Coverage: 91%
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)
Download this entry's XML file (.xml)
Download this entry's JSON file (.json)
